The sex prevalence of lower limb varicose vein networks.

OBJECTIVE: To determine the sex prevalence of lower limb varicose networks fed by reflux of the great saphenous vein (GSV), anterior accessory saphenous vein (AASV) and small saphenous vein (SSV) singularly or in combinations. METHODS: We scanned by the means of the same Colour Doppler Sonography (CDS) protocol 3000 lower limbs in 1500 consecutive patients, affected by symptomatic chronic venous insufficiency (CVI) during the decade 2013-2023. Limbs with normal venous function, incomplete scans or affected by post thrombotic syndrome, pelvic reflux, venous malformation, phlebolymphedema and CEAP clinical class C5-C6 were excluded from the final analysis. RESULTS: Overall, 1072 patients, 252 (23.5%) males and 820 (76.5%) females (p<0.0001), matched for age (p=0.692), were included into the study for a total of 1956 limbs affected by primary CVI, clinical class C2-C4. The main finding was the significant prevalence of varicose networks fed by reflux of the AASV alone (OR 1.96, CI 1.26-3.06, p=0.001) or combined with GSV (OR 1.84, CI 1.34-2.52, p=0.0002) in females. On the other hand, GSV insufficiency alone was significantly prevalent in males (OR 0.54, CI 0.43-0.68, p<0.0001). Moreover, we considered the presence of competent terminal valve (TV+) at the level of the sapheno-femoral junction, which resulted more significantly present in female (OR 1.57, CI 1.12-2.19, p=0.0083); to the contrary incompetent terminal valve (TV-) was more common in males (OR 0.64, CI 0.46-0.89, p=0.0083). Finally, considering reflux in the AASV territory in presence of a TV+, a strong prevalence in females was detected (OR 2.28, CI 1.48-3.52, p=0.0002), while males developed reflux along the GSV when a concomitant TV- was present (OR 0.62, CI 0.41-0.94, p =0.0244). CONCLUSIONS: The analysis of the lower limb varicose networks highlights that reflux along the AASV alone, in presence of a competent terminal valve at the junction, or coupled with GSV insufficiency, is more prevalent in females. On the other hand, GSV resulted the main trunk feeding varicose veins in males, in particular when an incompetent terminal valve was detected. Our findings suggest that females could be more prone to develop the varicose vein with an ascending mechanism, whereas in males the descending one seems more common.

Long-Term Efficacy of Ultrasound-Guided Percutaneous Transluminal Angioplasty for Arteriovenous Fistula Outflow Stenosis Caused by Venous Valve.

Introduction: Venous valve-related stenosis (VVRS) is an uncommon type of failure of arteriovenous fistula among patients with end-stage renal disease (ESRD). There is a paucity of data on the long-term efficacy of ultrasound-guided percutaneous transluminal angioplasty (PTA) for VVRS. Methods: ESRD patients who underwent PTA because of VVRS between January 2017 and December 2021 at the First Affiliated Hospital of Chongqing Medical University were enrolled. Patients were classified into three cohorts (cohort1, VVRS located within 3 cm of the vein adjacent to the anastomosis; cohort2, VVRS located over 3 cm away from the anastomosis; cohort3, multiple stenoses). The patency rates were assessed by the Kaplan-Meier method and compared using the log-rank test. Univariate and multivariate Cox analyses were performed to identify the risk factors. Results: A total of 292 patients were enrolled, including 125 (42.8%), 111 (38.0%), and 56 (19.2%) patients in cohort1, cohort2, and cohort3, respectively. The median follow-up was 34.8 months. The 6-month, 1-year, 2-year, and 3-year primary patency rates were 86.0%, 69.4%, 47.5%, and 35.3%, respectively. The secondary patency rates were 94.5%, 89.4%, 75.5%, and 65.3%, respectively. Cohort1 showed a relatively better primary patency compared to cohort2 and cohort3. The secondary patency rates were comparable in the three cohorts. Duration of dialysis and VVRS type were potential factors associated with primary patency. Conclusions: This study showed acceptable long-term primary and secondary patency rates after PTA for VVRS in ESRD patients, especially for those with VVRS located within 3 cm of the vein adjacent to the anastomosis.

The effect of ultrasound-assisted thrombolysis studied in blood-on-a-chip.

BACKGROUND: Thromboembolism, which leads to pulmonary embolism and ischemic stroke, remains one of the main causes of death. Ultrasound-assisted thrombolysis (UAT) is an effective thrombolytic method. However, further studies are required to elucidate the mechanism of ultrasound on arterial and venous thrombi. METHODS: We employed the blood-on-a-chip technology to simulate thrombus formation in coronary stenosis and deep vein valves. Subsequently, UAT was conducted on the chip to assess the impact of ultrasound on thrombolysis under varying flow conditions. Real-time fluorescence was used to assess thrombolysis and drug penetration. Finally, scanning electron microscopy and immunofluorescence were used to determine the effect of ultrasound on fibrinolysis. RESULTS: The study revealed that UAT enhanced the thrombolytic rate by 40% in the coronary stenosis chip and by 10% in the deep venous valves chip. This enhancement is attributed to the disruption of crosslinked fibrin fibers by ultrasound, leading to increased urokinase diffusion within the thrombus and accumulation of plasminogen on the fibrinogen α chain. Moreover, the acceleration of the dissolution rate of thrombi in the venous valve chip by ultrasound was not as significant as that in the coronary stenosis chip. CONCLUSION: These findings highlight the differential impact of ultrasound on thrombolysis under various flow conditions and emphasize the valuable role of the blood-on-a-chip technology in exploring thrombolysis mechanisms.

Endovenous thermal ablation of superficial truncal veins and compression therapy result in symptom relief in venous valve aplasia.

Venous valve aplasia (or valvular rarefication) is a rare cause of chronic venous insufficiency. In the present report, we have described the case of a 33-year-old man with severe symmetric lower leg edema and heaviness and pain in both lower legs. Duplex ultrasound demonstrated severe venous insufficiency in the superficial and deep venous system of both legs. Further imaging examinations supported the diagnosis of venous valvular aplasia. Treatment consisted of endovenous thermal ablation of the great saphenous vein and small saphenous vein as well as consistent compression therapy, resulting in a marked reduction of his leg edema, heaviness, and pain.

Numerical simulation and experimental validation of thrombolytic therapy for patients with venous isomer and normal venous valves.

Thrombus is an extremely dangerous factor in the human body that can block the blood vessel. Once thrombosis happens in venous of lower limbs, local blood flow is impeded. This leads to venous thromboembolism (VTE) and even pulmonary embolism. In recent years, venous thromboembolism has frequently occurred in a variety of people, and there is no effective treatment for patients with different venous structures. For the patients with venous isomer with single valve structure, we establish a coupled computational model to simulate the process of thrombolysis with multi-dose treatment schemes by considering the blood as non-Newtonian fluid. Then, the corresponding in vitro experimental platform is built to verify the performance of the developed mathematical model. At last, the effects of different fluid models, valve structures and drug doses on thrombolysis are comprehensively studied through numerical and experimental observations. Comparing with the experimental results, the relative error of blood boosting index (BBI) obtained from non-Newtonian fluid model is 11% smaller than Newtonian fluid. In addition, the BBI from venous isomer is 1300% times stronger than patient with normal venous valve while the valve displacement is 500% times smaller. As consequence, low eddy current and strong molecular diffusion near the thrombus in case of isomer promote thrombolysis rate up to 18%. Furthermore, the 80 µM dosage of thrombolytic drugs gets the maximum thrombus dissolution rate 18% while the scheme of 50 µM doses obtains a thrombolysis rate of 14% in case of venous isomer. Under the two administration schemes for isomer patients, the rates from experiments are around 19.1% and 14.9%, respectively. It suggests that the proposed computational model and the designed experiment platform can potentially help different patients with venous thromboembolism to carry out clinical medication prediction.

Two-Year Results of a First-In-Human Study in Patients Surgically Implanted With a Bioprosthetic Venous Valve, the VenoValve in Patients With Severe Chronic Venous Insufficiency.

OBJECTIVE: Two-year follow-up results from a first-in-human study of patients implanted with the VenoValve are evaluated for supporting the long-term clinical safety and performance of the device. BACKGROUND: Chronic Venous Insufficiency (CVI) involves improper functioning of lower limb vein valves and inability of these valves to move blood back towards the heart. CVI symptoms include swelling, varicose veins, pain, and leg ulcers. Currently, there is no cure for this condition and treatment options are limited. This study provides 2-year outcomes for 8 patients who were implanted with the bioprosthetic VenoValve for treating severe CVI with deep venous reflux measured at the mid-popliteal vein. The 6-month and 1-year results were previously published. METHODS: Eleven patients with C5 & C6 CVI were implanted with VenoValve into the midthigh femoral vein and followed for 2 years. Assessed clinical outcomes include device-related adverse events, reflux time, disease severity, and pain scores. RESULTS: All 11 implant procedures were successful. Two-year follow-up data was obtained for 8 subjects: 1 patient died of non-device related causes, 1 was lost to follow-up, and 1 refused to follow-up due to the COVID-19 pandemic. No device-related adverse events occurred between the first and second years of follow-up. Reported 2-year clinical performance outcomes included significant decreases in mean reflux times of the mid-popliteal vein (61%), and significant improvements in mean scores for disease severity rVCSS (56%) and VAS pain (87%). CONCLUSIONS: Results from this study support long-term safety and effectiveness of the VenoValve for improving CVI severity by reducing reflux and thereby venous pressures in the lower extremities. With limited treatments for valvular incompetence involved in severe, deep venous CVI, the device may be considered as a novel therapy. A pivotal trial in the United States is currently being conducted to assess the device in a larger number of patients.

Usefulness of aliasing phenomenon for diagnosing venous valve stenosis of arteriovenous fistula in a hemodialysis patient.

We present venous valve stenosis, which is an uncommon cause of arteriovenous fistula (AVF) dysfunction. Owing to the thin structure in echography, venous valves are challenging to observe; however, we have found that the aliasing phenomenon is useful for diagnosing venous valve stenosis.

Persistent right venous valve as a cause of fetal and neonatal pathology from prenatal to postnatal periods: a case report and review.

Background: Neonatal cyanosis is a clinical manifestation of hypoxemia and is usually pathological. Persistent right venous valve (PRVV) is a rare cause of cyanosis in newborns and can cause prenatal abnormalities, the clinical significance of which varies depending on the severity of the abnormality. There have been few reports on the intrauterine detection of these abnormalities and their follow-up during infancy. Here, we report a case of PRVV causing supravalvular tricuspid valve (TV) obstruction and secondary right ventricle (RV) hypoplasia. This case is unique in terms of its early prenatal detection, distinct cardiac anomalies, and successful surgery that reversed the symptoms, and the findings offer insights into the diagnosis and management of such rare cardiac conditions. Case Description: We report a case of a newborn diagnosed with PRVV at 31 weeks of gestation at our center. There was no underlying family history of congenital heart disease. Prenatal sonography identified an echogenic membrane in the right atrium, suggesting TV obstruction and subsequent RV hypoplasia. After birth, the neonate suffered hypoxia with decreased arterial oxygen saturation (SaO2). Minimally invasive surgery successfully corrected the membrane. Postoperative SaO2 improved immediately. Three months later, follow-up echocardiography revealed normalized TV and RV dimensions. The patient demonstrated steady progress without any complications. We also reviewed previous cases of PRVV before and after birth and summarized the sonographic and clinically relevant features. Conclusions: Although PRVV is typically considered as a benign structure, it may lead to significant clinical complications, particularly in fetuses and neonates. The precise identification of its variant forms and related flow patterns is crucial to inform decisions regarding patient management.

Efficacy of the microscopic parachute end-to-side technique for creating large-to-small venous anastomoses in free flaps in the extremities.

Purpose: The availability of reliable and suitably sized veins is limited for creating free flaps to treat severe trauma and infection, and it is important to manage vessel size discrepancy between the recipient and flap veins. We evaluated the clinical outcomes of free flaps with large-to-small venous end-to-side (ETS) anastomoses using the microscopic parachute end-to-side (MPETS) anastomosis in soft tissue defects in the extremities. This procedure comprises mainly a wide-slit venotomy and parachute procedure at the heel. Methods: We examined 24 free flaps in 23 patients given a large-to-small venous anastomosis using the MPETS technique. Patient demographics, details of vessel anastomoses, and flap outcomes and complications were obtained from medical records. Results: Two veins were anastomosed in six flaps. Thirty anastomosed veins were assessed, and 24 deep veins, all of which accompanied main arteries, were chosen as recipient veins. The mean diameters were 1.5 mm in the recipient veins and 2.7 mm in the flap veins, and the mean vessel size discrepancy was 1.8-fold (range 1.3-3.3 fold). Because of the presence of venous valves at the anastomotic site, trimming of venous cusps was performed in six veins. All flaps survived, though one venous thrombosis occurred because of pedicle kinking in a case with a short pedicle. Conclusions: The MPETS technique is simple, reliable, and useful for performing various types of venous anastomoses regardless of a vessel size discrepancy and the presence of a venous valve. This may be a good option for large-to-small venous anastomosis in free flaps.

Glutaraldehyde fixation of venous valve tissue: A benchmark for alternative fixation methods.

OBJECTIVE: Bioprosthetic venous valves have yet to achieve long-term patency due to issues with calcification following implantation that is influenced by current xenograft fixation methods, most notably glutaraldehyde. The goal of this study was to investigate the effects of glutaraldehyde fixation on the functional properties of venous tissue to establish a benchmark for the evaluation of alternative fixation methods. METHODS: The degree of crosslinking was evaluated by determining shrink temperature and the stability of tissue with pronase and collagenase digestion. RESULTS: Glutaraldehyde fixation of venous tissue was confirmed by a significant difference in the shrink temperature between fresh and glutaraldehyde treated samples. Significant differences in the amount of tissue remaining following digestion were observed for venous versus cardiac tissue. CONCLUSIONS: This study demonstrates the importance of tissue-specific evaluation in the development of alternative xenograft fixation methods to improve outcomes with bioprosthetic venous valves.

One-Year First-in-Human Success for VenoValve in Treating Patients With Severe Deep Venous Insufficiency.

OBJECTIVE: The clinical outcomes of this first-in-human (FIH) study provide safety and performance results 1 year after implantation of the VenoValve. BACKGROUND: Chronic venous insufficiency (CVI) is most often caused by valve failure in the venous system, which circulates blood from the lower limbs back to the heart and lungs. Severe diseases significantly influence quality of life, and current treatment options are limited. This study provides 1-year patient outcomes from 11 patients implanted with the VenoValve for treatment of severe deep venous CVI in C5 and C6 patients. Earlier results from 6-month follow-ups were previously published. METHODS: This prospective FIH study assessed the safety and performance of the VenoValve surgically implanted in 11 patients with C5 and C6 disease. All patients were followed up for at least 1 year. Assessments for adverse events, reflux time, disease severity, pain scores, and quality of life were reported. RESULTS: Implantation of VenoValve into the deep femoral vein was successful in all patients. Adverse events included 1 hematoma, 3 superficial wound infections, and 1 bleeding complication due to over-anticoagulation. One VenoValve became occluded due to patient non-compliance with anticoagulation medication. One-year clinical outcomes included significant decreases in mean reflux times (54%), and significant improvements in mean disease severity revised venous clinical severity score (56%), mean visual analog scale pain scores (76%), and Venous Insufficiency Epidemiologic and Economic Study QOL/sym scores. CONCLUSIONS: The promising results from this FIH study demonstrate sustained safety and effectiveness of the VenoValve at 1 year post-implantation, and support further study for its use as a novel treatment for severe, deep venous CVI caused by valvular incompetence. A pivotal, prospective, non-blinded, single-arm, multi-center study in the United States with seventy-five (75) patients is in progress to assess the safety and effectiveness of VenoValve in these patients through 30 days and 6 months. The clinical trial is registered on ClinicalTrials.gov under identifier: NCT04943172 (https://clinicaltrials.gov/ct2/show/NCT04943172?term=hancock+jaffe&draw=2&rank=1).

In silico analyses of blood flow and oxygen transport in human micro-veins and valves.

BACKGROUND: Almost 95% of the venous valves are micron scale found in veins smaller than 300µm diameter. The fluid dynamics of blood flow and transport through these micro venous valves and their contribution to thrombosis is not yet well understood or characterized due to difficulty in making direct measurements in murine models. OBJECTIVE: The unique flow patterns that may arise in physiological and pathological non-actuating micro venous valves are predicted. METHODS: Computational fluid and transport simulations are used to model blood flow and oxygen gradients in a microfluidic vein. RESULTS: The model successfully recreates the typical non-Newtonian vortical flow within the valve cusps seen in preclinical experimental models and in clinic. The analysis further reveals variation in the vortex strengths due to temporal changes in blood flow. The cusp oxygen is typically low from the main lumen, and it is regulated by systemic venous flow. CONCLUSIONS: The analysis leads to a clinically-relevant hypothesis that micro venous valves may not create a hypoxic environment needed for endothelial inflammation, which is one of the main causes of thrombosis. However, incompetent micro venous valves are still locations for complex fluid dynamics of blood leading to low shear regions that may contribute to thrombosis through other pathways.

Surgical repair of a special category of arteriovenous fistula outflow stenosis caused by venous valve hyperplasia.

OBJECTIVE: This study evaluated a special category of arteriovenous fistula outflow stenosis caused by venous valve hyperplasia and explored the effectiveness of surgical repair in dealing with this kind of stenosis. STUDY DESIGN: This retrospective cohort study was conducted from February 2016 to January 2020 in our center. Patients with arteriovenous fistula dysfunction, including flow rate insufficiency, venous hypertension, thrombosis, and aneurysm dilation enlargement, were selected. Stenosis lesions presenting with venous valve hyperplasia were selected after ultrasound screening. All patients underwent surgical repair and were followed up every 6 months after surgery. RESULTS: Forty-three patients (median age, 54.5 ± 11.2 years; 65.1% men) were included. All procedures were technically successful. Based on intraoperative exploration, 56.5% were reconstructed via autologous vein patch, 17.4% of patients were reconstructed with end-to-end reconstruction after cutting the stenotic segment, 13.0% of cases simply had the valve resected, and 13.0% of cases involved a longitudinal incision and transverse suture. All patients returned to routine dialysis the following day and avoided catheter insertion. The mean follow-up time was 22.5 ± 14.0 (range, 1.3-49.8) months. The patency rates at 2 and 4 years were 92.2% and 79.0%, respectively. Valves harvested from patients were analyzed via Masson staining and immunohistochemical staining, indicating collagen fiber and myofibroblast hyperplasia in outflow venous valve hyperplasia (OVVH). CONCLUSIONS: Outflow venous valve hyperplasia can lead to fistula dysfunction. Ultrasound is the main method to diagnosis OVVH. Special surgical repair can preserve valuable vascular resources and relieve stenosis, is safe and effective, and has a high patency rate.

Persistent Right Venous Valve: Insights From Multimodality Imaging.

Anatomic variants in the right atrium are under-recognized and under-reported phenomena in cardiac imaging. In the fetus, right atrium serves as a conduit for oxygenated blood to be delivered to the left heart bypassing the right ventricle and the nonfunctional lungs. The anatomy in the fetal right atrium is designed for such purposeful circulation. The right and left venous valves are prominent structures in the fetal heart that direct inferior vena caval flow towards the foramen ovale. These anatomic structures typically regress and the foramen ovale closes after birth. However, the venous valves can persist leading to a range of anatomic, physiological, and pathological consequences in the adult. We describe various presentations of persistent venous valves, focusing on the right venous valve in this illustrated multimodality imaging article.

The perplexity of catheter-directed thrombolysis for deep venous thrombosis: the approaches play an important role.

The recent adjunctive catheter-directed thrombolysis (ATTRACT) trial rose a controversy about the treatment effect of catheter-directed thrombolysis (CDT) in deep venous thrombosis (DVT). In fact, most studies including the ATTRACT trial did not perform subgroup analysis of catheterization approaches. Different approaches would confound the conclusions. Therefore, a single-center retrospective analysis was performed to compare the differences between the antegrade (AGA) and retrograde (RGA) approaches. Total 217 DVT patients treated with CDT were enrolled from January 2010 to December 2017, with mean age of 55.3 years (67 received antegrade approach, 150 received retrograde approach). The clot burden reduction by segment was evaluated. The mean access establishment time and thrombolytic time were compared. The patency of the iliofemoral vein at 6 months was evaluated. The rate of PTS, quality of life and venous insufficiency were assessed at 1 year. AGA group showed better thrombolytic effect in popliteal and femoral vein than RGA group. The rate of iliofemoral clot burden reduction in RGA group was mostly at Grade II, while most were at Grade III in AGA group. The retrograde approach showed better thrombolysis effect in iliofemoral DVT than popliteal to iliac DVT. The RGA group reported longer mean access establishment time (5.4 ± 1.8 vs 27.0 ± 7.5 min, p < 0.001) and thrombolytic time (6.9 ± 1.5 days vs 6.8 ± 1.5 days, p = 0.586). At 6 months, RGA group had a lower rate of femoral vein patency (52.0% vs 89.6%, p < 0.001) and a higher rate of venous insufficiency (52.0% vs 29.9%, p < 0.001), compared with AGA group. Although there was no difference in the rate of PTS, the RGA group showed higher Villalta scores in the free and mild PTS. The antegrade approach was preferably recommended over the retrograde approach for CDT treatment.

Targeted gene expression analysis of human deep veins.

OBJECTIVE: Endothelial-derived molecules involved in thrombosis and hemostasis have been investigated mainly in arteries and in experimental animals. The actual presence and integral function of these molecules in the human deep venous system have received less attention. Our aim was to evaluate the expression of certain prothrombotic and antithrombotic genes in the normal human deep veins of the lower extremities. METHODS: Macroscopically intact and competent valve-containing segments of human deep veins were prospectively collected from patients who had undergone above-knee amputation. Vein samples were separated into four zones: zone 1, postvalve (downstream, proximal) vein wall; zone 2, the valve cusp; zone 3, prevalve (upstream, distal) vein wall; and zone 4, vein wall within the valve cusp (cusp removed). Real-time quantitative polymerase chain reaction for principal genes involved in coagulation, fibrinolysis, and inflammation was performed to quantify messenger RNA. Selected protein gene products were measured by the western blot assay. One additional valve-containing segment underwent mass spectrometry analysis to investigate global differences in the proteome between the study zones. RESULTS: Seventeen valve-containing vein segments were analyzed. Significant upregulation of antithrombotic (protein C receptor [PROCR], thrombomodulin [THBD], tissue factor pathway inhibitor [TFPI]), prothrombotic (con Willebrand factor [VWF]), and proinflammatory (selectin P [SELP], intercellular adhesion molecule 1 [ICAM1]) genes was found in the valve cusp compared with the vein wall (P < .05). PROCR and THBD demonstrated the highest level of upregulation in the valve cusp. PROCR, serpin peptidase inhibitor, clade E, member 1 (SERPINE1), and SELP were upregulated in the valve cusp at the protein level (P < .05). Messenger RNA composition in the vein wall within the valve cusp was similar to the prevalve and postvalve vein wall for all genes, except for two times overexpressed ICAM1 (P < .05). Substantial differences within the proteome between the study zones were observed with mass spectrometry. CONCLUSIONS: The biological properties of the valve cusp, vein wall within the valve cusp, and vein wall beyond the valve cusp are different. The endothelium of the valve cusps of a normal competent deep venous valve may be naturally less thrombogenic compared with the vein wall. The endothelium of the valve cusp may have a higher potential to interact with white blood cells compared with the vein wall. Mass spectrometry demonstrates substantial differences in the proteome between the vein wall and the valve cusps that were not anticipated before. (J Vasc Surg Venous Lymphat Disord 2021;9:770-80.) CLINICAL RELEVANCE: Deep vein thrombosis (DVT) is a major cause of mortality, morbidity, and impaired quality of life. Multiple risk factors have been identified, although their relative weight and pathophysiologic interactions remain obscure. Many patients with multiple risk factors for DVT never develop this condition. Conversely, in numerous cases DVT cannot be attributed to any known clinical risk factor. The molecular mechanisms that initiate DVT are unclear. An improved understanding of the normal biology of human deep veins will serve as an important foundation for new hypotheses of the pathogenesis of DVT. The latter may suggest new projects on novel therapeutic strategies.

Microengineered Human Vein-Chip Recreates Venous Valve Architecture and Its Contribution to Thrombosis.

Deep vein thrombosis (DVT) and its consequences are lethal, but current models cannot completely dissect its determinants-endothelium, flow, and blood constituents-together called Virchow's triad. Most models for studying DVT forego assessment of venous valves that serve as the primary sites of DVT formation. Therefore, the knowledge of DVT formed at the venous cusps has remained obscure due to lack of experimental models. Here, organ-on-chip methodology is leveraged to create a Vein-Chip platform integrating fully vascularized venous valves and its hemodynamic, as seen in vivo. These Vein-Chips reveal that vascular endothelium of valve cusps adapts to the locally disturbed microenvironment by expressing a different phenotype from the regions of uniform flow. This spatial adaptation of endothelial function recreated on the in vitro Vein-Chip platform is shown to protect the vein from thrombosis from disturbed flow in valves, but interestingly, cytokine stimulation reverses the effect and switches the valve endothelium to becoming prothrombotic. The platform eventually modulates the three factors of Virchow's triad and provides a systematic approach to investigate the determinants of fibrin and platelet dynamics of DVT. Therefore, this Vein-Chip offers a new preclinical approach to study venous pathophysiology and show effects of antithrombotic drug treatment.

Fluid-structure interaction of blood flow around a vein valve.

Introduction: Venous valves are a type of one-way valves which conduct blood flow toward the heart and prevent its backflow. Any malfunction of these organs may cause serious problems in the circulatory system. Numerical simulation can give us detailed information and point to point data such as velocity, wall shear stress, and von Mises stress from veins with small diameters, as obtaining such data is almost impossible using current medical devices. Having detailed information about fluid flow and valves' function can help the treatment of the related diseases. Methods: In the present work, the blood flow through a venous valve considering the flexibility of the vein wall and valve leaflets is investigated numerically. The governing equations of fluid flow and solid domain are discretized and solved by the Galerkin finite element method. Results: The obtained results showed that the blood velocity increases from inlet to the leaflets and then decreases passing behind the valve. A pair of vortices and the trapped region was observed just behind the valves. These regions have low shear stresses and are capable of sediment formation. Conclusion: The von Mises stress which is a criterion for the breakdown of solid materials was obtained. It was also observed that a maximum value occurred at the bottom of the leaflets.