D-dimer levels and risk of recurrence following provoked venous thromboembolism: findings from the RIETE registry.

BACKGROUND: Patients with venous thromboembolism (VTE) secondary to transient risk factors may develop VTE recurrences after discontinuing anticoagulation. Identifying at-risk patients could help to guide the duration of therapy. METHODS: We used the RIETE database to assess the prognostic value of d-dimer testing after discontinuing anticoagulation to identify patients at increased risk for recurrences. Transient risk factors were classified as major (postoperative) or minor (pregnancy, oestrogen use, immobilization or recent travel). RESULTS: In December 2018, 1655 VTE patients with transient risk factors (major 460, minor 1195) underwent d-dimer measurements after discontinuing anticoagulation. Amongst patients with major risk factors, the recurrence rate was 5.74 (95% CI: 3.19-9.57) events per 100 patient-years in those with raised d-dimer levels and 2.68 (95% CI: 1.45-4.56) in those with normal levels. Amongst patients with minor risk factors, the rates were 7.79 (95% CI: 5.71-10.4) and 3.34 (95% CI: 2.39-4.53), respectively. Patients with major risk factors and raised d-dimer levels (n = 171) had a nonsignificantly higher rate of recurrences (hazard ratio [HR]: 2.14; 95% CI: 0.96-4.79) than those with normal levels. Patients with minor risk factors and raised d-dimer levels (n = 382) had a higher rate of recurrences (HR: 2.34; 95% CI: 1.51-3.63) than those with normal levels. On multivariate analysis, raised d-dimers (HR: 1.74; 95% CI: 1.09-2.77) were associated with an increased risk for recurrences in patients with minor risk factors, not in those with major risk factors. CONCLUSIONS: Patients with raised d-dimer levels after discontinuing anticoagulant therapy for VTE provoked by a minor transient risk factor were at an increased risk for recurrences.

Nitric Oxide Deficit Drives Intimal Hyperplasia in Mouse Models of Hypertension.

OBJECTIVE: To evaluate the impact of different types of hypertension on the development of intimal hyperplasia (IH). METHOD: Genetic, surgical, and pharmacological models of hypertension were used to compare IH formation in a murine model of carotid artery ligation (CAL). CAL was performed in normotensive WT male mice and in three mouse models of hypertension: (1) L-NAME (Nω-nitro-l-arginine-methyl-ester) treatment for 2 weeks prior to CAL to instate renin-independent hypertension; (2) 2K1C (two kidneys, one clip) surgery 1 week prior to CAL to induce renin-dependent hypertension; (3) Cx40-/- mice, a genetic model of renin-dependent hypertension. Mice were sacrificed prior to CAL or 3, 14, or 28 days post CAL. Data collection included tail blood pressure measurements, and morphometric and histological assessment of the ligated carotids. RESULTS: CAL triggered the formation of a VSMC-rich neointima layer after 14-28 days, which was increased in all hypertensive mice. Despite similarly increased blood pressure, L-NAME treated mice displayed more IH than all other hypertensive groups. In addition, L-NAME induced hypertension triggered more cell proliferation and recruitment of CD45 positive inflammatory cells to the ligated vessel wall compared with Cx40-/- or normotensive WT mice. CONCLUSIONS: NO deficiency is a major aspect of vascular inflammation, VSMC proliferation, and IH in hypertensive conditions.

[Treatment of critical lower limb ischemia]. / Traitement de l'ischémie critique chronique des membres inférieurs en 2014.

Critical limb ischemia is a major public health problem in our western countries due to the epidemia of (diabesity). The outcome of patients suffering from critical limb ischemia reains poor with an amputation free survival rate at one year of about 50%. The treatment should be multidiciplinary and done in emergency in specialized centers to ensure the limb salvage: this management should be centered aroud 3 axis: the screening of the cardiovascular risk factors, the best medical treatment and the invasive approaches. Due to multiple endovascular technical innovations, more frail patients with com plex diseases can be treated with good results. Therefore, the endovascular treatment is essential in the management of such patients by vascular surgeons.

[Popliteal artery entrapment syndrome]. / Syndrome de l'artère poplitée piégée.

Popliteal entrapment is a rare compression syndrome involving vascular (and neurologic) structures of the popliteal fossa. In this article we review the popliteal artery entrapment syndrome (PAES). PAES is a cause of intermittent claudication that can be, although rarely, complicated with acute limb-threatening ischemia. PAES occurs more often in young adult. Concerning pathophysiology, PAES is provoked by an abnormal relationship between popliteal artery and muscular-tendon structures within the popliteal fossa. A surgical repair is usually required to resolve mechanical compression or vascular damage.

Multimodality imaging in thoracic aortic diseases: a clinical consensus statement from the European Association of Cardiovascular Imaging and the European Society of Cardiology working group on aorta and peripheral vascular diseases.

Imaging techniques play a pivotal role in the diagnosis, follow-up, and management of aortic diseases. Multimodality imaging provides complementary and essential information for this evaluation. Echocardiography, computed tomography, cardiovascular magnetic resonance, and nuclear imaging each have strengths and limitations in the assessment of the aorta. This consensus document aims to review the contribution, methodology, and indications of each technique for an adequate management of patients with thoracic aortic diseases. The abdominal aorta will be addressed elsewhere. While this document is exclusively focused on imaging, it is of most importance to highlight that regular imaging follow-up in patients with a diseased aorta is also an opportunity to check the patient's cardiovascular risk factors and particularly blood pressure control.

[Prevention of post-thrombotic syndrome]. / Prévention du syndrome post-thrombotique.

Post-thrombotic syndrome (PTS) is the most frequent chronic complication of deep vein thrombosis (DVT) with an estimated prevalence of 30-50%. PTS is a significant cause of disability, especially when complicated by venous ulcers. Therefore, PTS has important socio-economic consequences for both the patient and the health care system. Actually, the efficacy of PTS treatment is very limited; therefore, best treatment remains prevention. Compression therapy, particularly by graduated compression stockings (GCS) has a pivotal role in PTS prophylaxis. Aim of this article is to resume state of the art literature on this subject. Recommendations on PTS prevention have even been reported.

[Vascular rehabilitation of patients suffering from peripheral arterial disease]. / Rééducation vasculaire du patient artériopathe.

Rehabilitation programs represent an important and valuable tool for patients suffering various diseases. Supervised exercise programs for patients with peripheral arterial diseases have been shown to be efficacious in ameliorating walking performances and quality of life of such patients. With this regards the angiology service of the CHUV in Lausanne has established a multidisciplinary supervised program of vascular rehabilitation. This article describes organisation and characteristics of such a program.

[Prevention of chronic venous disease: which advice for our patients?]. / Prévention de la maladie veineuse chronique: quels conseils donner à nos patients?

Chronic venous disease (CVD) is a major public health problem due to its high prevalence and socioeconomic costs. In absence of adequate care, it can lead to chronic venous insufficiency (CVI). Disturbed venous-flow patterns lead to venous hypertension. Therefore, prevention of CVD involves venous hypertension reduction. In primary prevention, it is essential to inform the patient about necessary lifestyle changes. In case of CVD, it is essential to propose treatment (compression, venoactive drugs, and interventional treatments) to avoid CVI appearance and eventually offer the best therapy solutions for CVI complications.

[Lymphatic disorders and prevention of their complications]. / Prévention des troubles lymphatiques et de leurs complications.

The prevalence of lymphedema is clearly underestimated. Too few patients receive treatment. It requires several specifically trained participants and must be conceived in the long term given the chronic nature and the incurability of this pathology. Prevention is therefore of major importance. Successfully applied to operated women for breast cancer, other models of coverage deserve to be developed to reduce the incidence of lymphedema and its complications, particularly after oncologic, orthopedic and vascular surgery and for patients affected by venous insufficiency.

[Vascular follow up in patients suffering from peripheral arterial disease and undergoing revascularization]. / Suivi angiologique des patients artériopathes après geste de revascularisation.

The rapid evolution of revascularization techniques has allowed an improvement in quality of life of patients with peripheral artery disease. The angiological follow-up aims to insure durable results of revascularization, to diminish risk of amputation and to limit progression of atheroma plaques. The patient history and physical examination are essential in evaluating impact of peripheral artery disease upon quality of life and insuring the appropriate control of cardiovascular risk factors.

[Superficial vein thrombosis: what's new in the management?]. / Thrombose veineuse superficielle: quelles nouveautés dans la prise en charge?

Lower limbs superficial venous thrombosis (SVT) is a relatively frequent disease. Its prevalence among patients consulting their treating physician is estimated to be 10.8% among women and 4.9% among men. Up to 25% of at risk patients with isolated SVT present with a concomitant DVT. Ultrasound imaging may play a role in the management of these patients allowing precise diagnosis, determination of thrombus extension and presence of associated DVT. From data recently appeared in the literature treatment of SVT with prophylactic doses of fondaparinux may be proposed to at risk patients with isolated SVT.

Lack of prophylaxis before the onset of acute venous thromboembolism among hospitalized cancer patients: the SWIss Venous ThromboEmbolism Registry (SWIVTER).

BACKGROUND: Venous thromboembolism (VTE) prophylaxis remains underutilized, particularly in cancer patients. We explored clinical predictors of prophylaxis in hospitalized cancer patients before the onset of acute VTE. METHODS: In the SWiss Venous ThromboEmbolism Registry, 257 cancer patients (61 +/- 15 years) with acute VTE and prior hospitalization for acute medical illness or surgery within 30 days (91% were at high risk with Geneva VTE risk score > or =3) were enrolled. RESULTS: Overall, 153 (60%) patients received prophylaxis (49% pharmacological and 21% mechanical) before the onset of acute VTE. Outpatient status at the time of VTE diagnosis [odds ratio (OR) 0.31, 95% confidence interval (CI) 0.18-0.53], ongoing chemotherapy (OR 0.51, 95% CI 0.31-0.85), and recent chemotherapy (OR 0.53, 95% CI 0.32-0.88) were univariately associated with the absence of VTE prophylaxis. In multivariate analysis, intensive care unit admission within 30 days (OR 7.02, 95% CI 2.38-20.64), prior deep vein thrombosis (OR 3.48, 95% CI 2.14-5.64), surgery within 30 days (OR 2.43, 95% CI 1.19-4.99), bed rest >3 days (OR 2.02, 95% CI 1.08-3.78), and outpatient status (OR 0.38, 95% CI 0.19-0.76) remained the only independent predictors of thromboprophylaxis. CONCLUSIONS: Although most hospitalized cancer patients were at high risk, 40% did not receive any prophylaxis before the onset of acute VTE. There is a need to improve thromboprophylaxis in cancer patients, particularly in the presence of recent or ongoing chemotherapy.

Ex vivo pulsatile perfusion of human saphenous veins induces intimal hyperplasia and increased levels of the plasminogen activator inhibitor 1.

Vessel wall trauma induces vascular remodeling processes including the development of intimal hyperplasia (IH). To assess the development of IH in human veins, we have used an ex vivo vein support system (EVVSS) allowing the perfusion of freshly isolated segments of saphenous veins in the presence of a pulsatile flow which reproduced arterial conditions regarding shear stress, flow rate and pressure during a period of 7 and 14 days. Compared to the corresponding freshly harvested human veins, histomorphometric analysis showed a significant increase in the intimal thickness which was already maximal after 7 days of perfusion. Expression of the endothelial marker CD31 demonstrated the presence of endothelium up to 14 days of perfusion. In our EVVSS model, the activity as well as the mRNA and protein expression levels of plasminogen activator inhibitor 1, the inhibitor of urokinase-type plasminogen activator (uPA) and tissue-type plasminogen activator (tPA), were increased after 7 days of perfusion, whereas the expression levels of tPA and uPA were not altered. No major change was observed between 7 and 14 days of perfusion. These data show that our newly developed EVVSS is a valuable setting to study ex vivo remodeling of human veins submitted to a pulsatile flow.

Long-term outcomes of elderly patients with CYP2C9 and VKORC1 variants treated with vitamin K antagonists.

Essentials The long-term effects of VKORC1 and CYP2C9 variants on clinical outcomes remains unclear. We followed 774 patients ≥65 years with venous thromboembolism for a median duration of 30 months. Patients with CYP2C9 variants are at increased risk of death and non-major bleeding. Patients with genetic variants have a slightly lower anticoagulation quality only. SUMMARY: Background The long-term effect of polymorphisms of the vitamin K-epoxide reductase (VKORC1) and the cytochrome P450 enzyme gene (CYP2C9) on clinical outcomes remains unclear. Objectives We examined the association between CYP2C9/VKORC1 variants and long-term clinical outcomes in a prospective cohort study of elderly patients treated with vitamin K antagonists for venous thromboembolism (VTE). Methods We followed 774 consecutive patients aged ≥ 65 years with acute VTE from nine Swiss hospitals for a median duration of 30 months. The median duration of initial anticoagulant treatment was 9.4 months. The primary outcome was the time to any clinical event (i.e. the composite endpoint of overall mortality, major and non-major bleeding, and recurrent VTE. Results Overall, 604 (78%) patients had a CYP2C9 or VKORC1 variant. Three hundred and thirty-four patients (43.2%) had any clinical event, 119 (15.4%) died, 100 (12.9%) had major and 167 (21.6%) non-major bleeding, and 100 had (12.9%) recurrent VTE. After adjustment, CYP2C9 (but not VKORC1) variants were associated with any clinical event (hazard ratio [HR], 1.34; 95% confidence interval [CI], 1.08-1.66), death (HR, 1.74; 95% CI, 1.19-2.52) and clinically relevant non-major bleeding (sub-hazard ratio [SHR], 1.39; 95% CI, 1.02-1.89), but not with major bleeding (SHR, 1.03; 95% CI, 0.69-1.55) or recurrent VTE (SHR, 0.95; 95% CI, 0.62-1.44). Patients with genetic variants had a slightly lower anticoagulation quality. Conclusions CYP2C9 was associated with long-term overall mortality and non-major bleeding. Although genetic variants were associated with a slightly lower anticoagulation quality, there was no relationship between genetic variants and major bleeding or VTE recurrence.

[The prognosis of pulmonary embolism: are there practical implications for patient management?]. / Etablir le pronostic de l'embolie pulmonaire: est-ce important pour la prise en charge?

There is growing evidence that outpatient treatment is safe and effective for many patients with non-massive pulmonary embolism. Despite this evidence, the vast majority of patients with non-massive pulmonary embolism continue to be treated in an inpatient setting. A major barrier to outpatient treatment has been the lack of explicit criteria to identify patients with pulmonary embolism at low-risk of adverse medical outcome. This article discusses new risk stratification tools for pulmonary embolism such as echocardiography, biomarkers, and clinical prognostic scores, and their potential application for patient management.

[Venous thromboembolic disease in adolescents]. / La thrombose veineuse profonde chez l'adolescent.

Deep vein thrombosis in children and adolescents is a quite rare event. Risk factors most often associated with DVT in this particular population are: central vein catheters, neoplasia, vascular malformations and oral contraception. Diagnosis and management of DVT in adolescents does not differ greatly from that of adults. Compression ultrasound is the initial exam of choice. Hospitalization is often not necessary and treatment can be started by using low molecular weight heparin followed by oral anti-vitamin K antagonists. Thrombophilia screening is not routinely recommended and should be reserved for those patients for whom results would change therapeutical management.

[Management of critical limb ischemia]. / Prise en charge de l'ischémie critique des membres inférieurs.

Critical limb ischemia (CLI) is the leading cause of major leg amputation. Diabetes, smoking and end stage renal disease are the main risk factors for CLI. Despite their reduced survival rate, most CLI patients should be treated by surgical or endovascular arterial reconstruction, since amputation rate with conservative treatment alone is as high as 95% at 1 year in surviving patients with tissue loss, and can be reduced to 25% with successful reconstruction. When arterial reconstruction is impossible or fails, spinal cord stimulation also allows to avoid major amputation in up to 75% of precisely selected patients. Timely management and multidisciplinary approach are advised to reduce the risk of major amputation.