Mutations in EPHB4 cause human venous valve aplasia.

Venous valve (VV) failure causes chronic venous insufficiency, but the molecular regulation of valve development is poorly understood. A primary lymphatic anomaly, caused by mutations in the receptor tyrosine kinase EPHB4, was recently described, with these patients also presenting with venous insufficiency. Whether the venous anomalies are the result of an effect on VVs is not known. VV formation requires complex "organization" of valve-forming endothelial cells, including their reorientation perpendicular to the direction of blood flow. Using quantitative ultrasound, we identified substantial VV aplasia and deep venous reflux in patients with mutations in EPHB4. We used a GFP reporter in mice to study expression of its ligand, ephrinB2, and analyzed developmental phenotypes after conditional deletion of floxed Ephb4 and Efnb2 alleles. EphB4 and ephrinB2 expression patterns were dynamically regulated around organizing valve-forming cells. Efnb2 deletion disrupted the normal endothelial expression patterns of the gap junction proteins connexin37 and connexin43 (both required for normal valve development) around reorientating valve-forming cells and produced deficient valve-forming cell elongation, reorientation, polarity, and proliferation. Ephb4 was also required for valve-forming cell organization and subsequent growth of the valve leaflets. These results uncover a potentially novel cause of primary human VV aplasia.

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.

Válvula venosa yugular interna como causa de dificultad para acceso venoso central / Internal jugular venous valve as a cause of difficult central venous access

La canulación venosa central es un procedimiento habitual en el medio hospitalario, siendo la vena yugular interna uno de los vasos más frecuentemente escogido para realizar el acceso venoso central. La presencia de válvulas venosas en dicha vena es un hecho conocido al que habitualmente no se concede importancia durante la canulación venosa central. No obstante, las válvulas venosas pueden llegar a dificultar este procedimiento, incrementando la probabilidad de que ocurran complicaciones. Presentamos el caso de un paciente en el cual la presencia de una válvula venosa yugular interna impidió obtener un acceso vascular a través de este vaso

Central venous cannulation is a commonly performed procedure in the hospital setting, while the internal jugular vein is one of the most frequently used to perform central venous access. The presence of venous valves in the jugular veins is a well-known fact, albeit often neglected during central venous cannulation. However, venous valves can make this procedure difficult, increasing the chance of developing complications. We report the case of a patient in whom the presence of a valve in the internal jugular vein did not permit a vascular access to be obtained through this vessel

High Resolution M-mode Evaluation of Jugular Vein Valves in Patients with Neurological and Neurosensory Disorders.

BACKGROUND: High prevalence of valve absence was found in the internal jugular vein (IJV) of healthy volunteers by means of M-mode high-resolution Echo Colour Doppler (ECD). However, the prevalence of valve in neurovascular disorders linked to Chronic Cerebrospinal Venous Insufficiency (CCSVI) is still unknown. METHODS: A cohort of 83 Healthy Controls (HC), 71 Multiple Sclerosis (MS), 99 Inner Ear Disorders (IED) underwent ECD investigation of the IJV valve, including M-mode evaluation and related hemodynamics. The primary outcome measure was characterization of valve presence, morphology and motility, whereas the secondary outcome was the rate of flow alteration. RESULTS: Bilateral valve presence was found in 38% of HC, 58% of MS and 25% of IED, whereas, bilateral valve absence was recorded in 16% of HC, 10% of MS and 31% of IED (p<0.003). Bicuspid morphology was more prevalent in HC 56%, while monocusp was more prevalent in patients: 75% MS and 57% IED (p<0.0001). The main finding was the presence of mobile valve leaflets in 98% of HC, contrarily fixed valve leaflets were recorded in 82% of MS and in 41% of IED, p< 0.0001. Finally, by stratifying the entire cohort according to the presence of mobile and not mobile valve leaflets, normal monodirectional and phasic flow were commonly found in the mobile leaflets subgroup, p<0.0001. CONCLUSION: In patients with miscellaneous neurological disorders, a significant higher rate of defective valves was found with respect to HC. The latter condition is strongly associated to brain outflow abnormalities described in CCSVI condition.

After Superficial Ablation for Superficial Reflux Associated with Primary Deep Axial Reflux, Can Variable Outcomes be Caused by Deep Venous Valve Anomalies?

OBJECTIVE: To identify which deep anatomical anomalies can explain variable hemodynamic outcomes in patients with superficial reflux associated with primary deep axial reflux who underwent isolated superficial vein ablation without improvement. METHODS: This is a retrospective study of deep venous valve anomalies in patients who underwent superficial vein ablation for superficial and associated deep reflux. A group of 21 patients who were diagnosed with saphenous reflux associated with primary deep axial reflux, were submitted to great saphenous vein ablation. In 17 patients the deep reflux was not abolished. In this subgroup, surgical exploration of the deep valve was carried out using venotomy for possible valve repair. RESULTS: Among the 17 subgroup patients, four post-thrombotic lesions were discovered intra-operatively in four patients; they underwent different surgical procedures. In 13 of the subgroup patients, primary valve incompetence was confirmed intra-operatively. In 11 cases the leaflets were asymmetrical and in only two were they symmetrical. After valvuloplasty, deep reflux was abolished in all 13 patients. Clinical improvement was obtained in 12/13 patients (92%). It is noteworthy that abolition of deep reflux was associated with significant improvement in air plethysmography data as well as with improvement in clinical status measured on CEAP class, VCSS and the SF-36 questionnaire. CONCLUSION: Failure to correct deep axial reflux by superficial ablation in patients with superficial and associated primary deep axial reflux may be related to asymmetry in the leaflets of the incompetent deep venous valve.

Differential Diagnosis and Clinical Implications of Remnants of the Right Valve of the Sinus Venosus.

Anatomic variants of the remnants of the right valve of the sinus venosus in adults are common and usually observed on cardiac imaging studies. Because the anatomy and function of these vestiges are not well known, errors may occur in the differential diagnosis and treatment of patients with unclear images in the right atrium. Clinical implications may arise from (1) differential diagnosis with some diseases, especially when the remnants act as sites of attachment for masses; (2) the need for invasive treatment if the anatomic variant displays obstructive behavior; (3) the association between remnants and patent foramen ovale; and (4) secondary complications related to these structures in invasive procedures. Thus, the aim of this review is to provide cardiologists and radiologists specializing in cardiac imaging techniques with the basic anatomic information and clinical implications required to understand morphologic variants of right sinus venosus valve vestiges in adults.

Absence of venous valves in mice lacking Connexin37.

Venous valves play a crucial role in blood circulation, promoting the one-way movement of blood from superficial and deep veins towards the heart. By preventing retrograde flow, venous valves spare capillaries and venules from being subjected to damaging elevations in pressure, especially during skeletal muscle contraction. Pathologically, valvular incompetence or absence of valves are common features of venous disorders such as chronic venous insufficiency and varicose veins. The underlying causes of these conditions are not well understood, but congenital venous valve aplasia or agenesis may play a role in some cases. Despite progress in the study of cardiac and lymphatic valve morphogenesis, the molecular mechanisms controlling the development and maintenance of venous valves remain poorly understood. Here, we show that in valved veins of the mouse, three gap junction proteins (Connexins, Cxs), Cx37, Cx43, and Cx47, are expressed exclusively in the valves in a highly polarized fashion, with Cx43 on the upstream side of the valve leaflet and Cx37 on the downstream side. Surprisingly, Cx43 expression is strongly induced in the non-valve venous endothelium in superficial veins following wounding of the overlying skin. Moreover, we show that in Cx37-deficient mice, venous valves are entirely absent. Thus, Cx37, a protein involved in cell-cell communication, is one of only a few proteins identified so far as critical for the development or maintenance of venous valves. Because Cxs are necessary for the development of valves in lymphatic vessels as well, our results support the notion of common molecular pathways controlling valve development in veins and lymphatic vessels.

Pre-pubertal presentation of peritoneal inclusion cyst associated with congenital lower extremity venous valve agenesis.

Peritoneal inclusion cysts are uncommon lesions that usually occur in the pelvis of reproductive-age females. The case of a 7-year-old girl with an inflamed peritoneal inclusion cyst with unusual right paracolic localization and congenital lower extremity superficial and deep venous valve agenesis is presented. Inflammation of the peritoneal inclusion cyst was responsible for the signs of acute abdomen and subsequent presentation at our center. The cystic structure was initially diagnosed using ultrasonography, and its complete extent (8cm x 6.5cm x 4cm) was evident after magnetic resonance imaging. The minimal access approach was opted for to resect the entire cyst from the lateral border of the ascending colon. Afterwards, the cyst was punctured to reduce its size and to retrieve the cyst wall using an endoscopic specimen retrieval bag. Minimal access surgery precautions in this patient with congenital lower extremity venous valve agenesis are discussed.

Neovalve construction in deep venous incompetence.

OBJECTIVES: The purpose of this study is to assess the outcome of neovalve construction in two consecutive series of patients affected by postthrombotic syndrome and valve agenesis. The technique was modified in the second series so as to correct a cause of failure. METHODS: Between December 2000 and June 2007, 40 neovalve constructions were carried out in 36 patients (19 males, 17 females, median age 57, range, 29-82) affected by deep venous insufficiency. Thirty-two patients were affected by postthrombotic syndrome and 4 by valve agenesis. The 32 patients with postthrombotic syndrome were selected from among 76 patients with resistant ulcers classified C (6,S) E (S) A (S,D,P) P (R,RO) and the 4 patients with valve agenesis were selected from among 28 affected by resistant ulcers classified as C (6,S) E (C) A (S,D,P) P (R). The patients were subdivided into 2 groups. The first group included 19 operations performed in the period between December 2000 and December 2004, with a median follow-up of 54 months (range, 31-78). The second group included 21 patients operated on between January 2005 and June 2007, with a median follow-up of 5 months (range, 2-29). In the second group, a surgical variation was applied in order to prevent flap collapse and to maintain the continence of the neovalve. RESULTS: In the first series, ulcer healing was observed in 16 cases out of 19 (84%). Recurrent ulcers were observed in one case after 3 years. Valve competence was ascertained in 13 cases per 803 patient-months (1.6/100 patient-months). With regard to the second series, competence was achieved in all cases with a cumulative rate of 21 per 228 patient-months (9.2/100 patient-months). In the second series, the ulcer failed to heal in one case and recurred in two cases, with an intention-to-treat ulcer recurrence rate of three cases per 209 patient-months. Postoperative deep-venous thrombosis was observed in 3 patients in the first series. None was detected in the second series. The mortality rate was 0 and in neither group was pulmonary embolism detected. CONCLUSION: The modified technique applied to the second group seemed to improve valve continence results significantly. However, a longer follow-up period is required for the latter group to validate this technical enhancement.

XI Congreso Nacional del capítulo de Flebología de la SEACV / No disponible

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