The paradigm shift in treatment of severe venous thromboembolism.

Pulmonary embolism (PE) is the third leading cause of cardiovascular death and the main cause of preventable in-hospital death in the world. The PERT® (Pulmonary Embolism Response Team) concept involves multidisciplinary diagnosis and immediate treatment. Deep venous thrombosis (DVT) is the initial cause of most cases of PE and is responsible for complications such as chronic thromboembolic recurrence, postthrombotic syndrome, and chronic thromboembolic pulmonary hypertension. An aggressive approach to severe cases of iliofemoral DVT similar to the PERT® system can not only reduce the immediate risk of PE and death but can also reduce later sequelae. New percutaneous techniques and mechanical thrombectomy devices for venous thromboembolism (VTE) have shown encouraging clinical results. We propose the development of an expanded concept of rapid response to VTE, which involves not only PE (PERT®) but also severe cases of DVT: the Venous Thromboembolism Response Team (VTERT®).

Association between the degree of iliac venous outflow obstruction by intravascular ultrasound and lower limb venous reflux.

OBJECTIVE: The present study aims to evaluate the association between the degree of iliac venous outflow obstruction (IVOO) identified by intravascular ultrasound (IVUS) and venous reflux presentation in the lower limbs on duplex ultrasound (DU). METHODS: Patients with bilateral chronic venous insufficiency, CEAP (clinical-etiology-anatomy-pathophysiology) C3 to C6, and a visual analog scale score for pain >5 underwent DU for reflux evaluation of the deep venous system (reflux ≥1 second); superficial system, great saphenous vein, and small saphenous vein (reflux ≥0.5 second); and perforator system (reflux ≥0.35 second). All patients underwent IVUS in the iliac venous territory. The area of the impaired venous segments was categorized as obstruction <50% (category 1), 50% to 79% (category 2), and ≥80% (category 3). The venous clinical severity score and reflux multisegment score (RMS) were assessed. RESULTS: A total of 51 patients (n = 102 limbs; age, 50.53 ± 14.5 years; 6 men) were included. The predominant clinical severity CEAP class was C3 in 54 of 102 limbs (52.9%). The mean VCSS was 14.3 ± 6.7. A severe RMS (≥3) was registered in 63.4% of the limbs. Of the 102 limbs, 51 (50%) presented with category 1, 27 (26.5%) with category 2, and 24 (23.5%) with category 3. Previous deep vein thrombosis (DVT) was associated with critical obstruction (odds ratio [OR], 3.65; 95% confidence interval [CI], 1.29-10.38; P = .015). The superficial and perforator venous systems had no association with the degree of IVOO. Deep venous reflux (DVR) had a significant association with significant IVOO (obstruction ≥50%; OR, 6.44; 95% CI, 2.19-18.93; P = .001) and critical IVOO (obstruction ≥80%; OR, 4.57; 95% CI, 1.70-12.27; P = .003) and a significant linear association with the IVOO degree and reflux in the femoral veins (P < .001) and popliteal vein (P = .008). Significant lesions were significantly more likely to develop in the left limb (OR, 5.76; 95% CI, 2.46-13.50; P < .001). After multivariate analysis, DVR remained a predictor for significant and critical obstruction (P < .003 and P < .012, respectively). Left limb and previous DVT remained as predictors for IVOO of ≥50% and ≥80% (P < .001 and P = .043, respectively). CONCLUSIONS: We found a significant linear association between the degree of IVOO and reflux in the deep venous system on DU. Limbs with DVR, a severe RMS, loss of respiratory variation on DU, and previous DVT were more likely to be affected by IVOO of ≥50%, especially with left leg involvement.

Comparison of computed tomography venography and intravascular ultrasound in screening and classification of iliac vein obstruction in patients with chronic venous disease.

OBJECTIVE: To investigate power of computed tomography venography (CTV) to identify and characterize iliac vein obstruction (IVO) compared with intravascular ultrasound (IVUS) examination in highly symptomatic patients with chronic venous disease (CVD). METHODS: CVD CEAP C3-6 limbs with visual analog scale for pain score of greater than 3 and/or Venous Clinical Severity Scale of greater than 8 were prospectively investigated with CTV and IVUS examination. The segment of maximum IVO was verified and categorically classified: group I, 0% to 49%; group II, 50% to 79%; and group III, 80% or greater. The CTV's screening power to detect the point and degree of maximum IVO was compared with IVUS. RESULTS: The CTV point of maximum IVO was 80% in the left limb, 10% in the right limb, 10% bilaterally; 2% in the inferior vena cava; 91% in the common iliac vein (CIV) confluence (41.6% below the CIV confluence, 34.5 at the CIV confluence, and 23.9% above the CIV confluence); 7% at the external iliac vein (kappa index 0.841; P < .001, when compared with IVUS). The distal venous segment considered free of obstruction was above inguinal ligament: 68% (CIV, 47%; external iliac vein, 21%) 32% below the inguinal ligament (common femoral vein, 26%; deep femoral vein, 6%) (kappa index 0.671; P = .023, when compared with IVUS). The power of CTV to detect an IVO of 50% or greater (groups II and III) when compared with IVUS achieved a sensitivity and specificity ratio of 94.0% and 79.2%, respectively. The positive predictive value was 94%, the negative predictive value was 79.1%, accuracy was 86.7% (kappa, 0.733), and interobserver agreement was 92.1% (95% confidence interval, 87.1-97.7; kappa, 0.899). CONCLUSIONS: CTV is a powerful screening method in determining the precise point of compression and classifying IVO in limbs with symptomatic CVD when compared with IVUS. The prevalence of an obstruction above the iliac vein confluence is significant and should be considered in iliac vein stenting treatment strategy. The tomographic classification system proposed here may help to define the optimum technique of treatment, prognosis, and comparison of outcome results.

A mudança de paradigma no tratamento do tromboembolismo venoso grave / The paradigm shift in treatment of severe venous thromboembolism

Resumo A embolia pulmonar (EP) é a terceira maior causa de morte cardiovascular e a principal de morte evitável intra-hospitalar no mundo. O conceito PERT® (do inglês, pulmonary embolism response team) envolve seu diagnóstico e tratamento precoce e multidisciplinar. A trombose venosa profunda (TVP) é a sua causa inicial na maioria dos casos e é responsável por complicações como a recidiva tromboembólica, a síndrome pós-trombótica e a hipertensão pulmonar tromboembólica crônica. Uma abordagem inicial semelhante ao PERT nos casos de TVP ilíaco-femoral grave pode reduzir não apenas o risco imediato de EP e morte, mas também suas sequelas tardias. Novas técnicas percutâneas e aparatos de trombectomia mecânica para o tromboembolismo venoso (TEV) vêm demonstrando resultados clínicos encorajadores. Propomos o desenvolvimento de um conceito ampliado de resposta rápida ao TEV, que envolve não apenas a EP (PERT®) mas também os casos graves de TVP: o time de resposta rápida para o TEV (TRETEV®), ou do inglês Venous Thromboembolism Response Team (VTERT®).

Abstract Pulmonary embolism (PE) is the third leading cause of cardiovascular death and the main cause of preventable in-hospital death in the world. The PERT® (Pulmonary Embolism Response Team) concept involves multidisciplinary diagnosis and immediate treatment. Deep venous thrombosis (DVT) is the initial cause of most cases of PE and is responsible for complications such as chronic thromboembolic recurrence, postthrombotic syndrome, and chronic thromboembolic pulmonary hypertension. An aggressive approach to severe cases of iliofemoral DVT similar to the PERT® system can not only reduce the immediate risk of PE and death but can also reduce later sequelae. New percutaneous techniques and mechanical thrombectomy devices for venous thromboembolism (VTE) have shown encouraging clinical results. We propose the development of an expanded concept of rapid response to VTE, which involves not only PE (PERT®) but also severe cases of DVT: the Venous Thromboembolism Response Team (VTERT®).

Analysis of threshold stenosis by multiplanar venogram and intravascular ultrasound examination for predicting clinical improvement after iliofemoral vein stenting in the VIDIO trial.

BACKGROUND: Selecting patients for iliofemoral vein stenting has traditionally relied on the identification and quantification of stenotic lesions with imaging such as multiplanar venography. Recently, intravascular ultrasound (IVUS) imaging has become more available. However, to date, the usefulness of these imaging modalities using the customary >50% treatment threshold for diameter (multiplanar venography) and area (IVUS) stenosis of iliofemoral veins has not been validated prospectively within the context of clinical improvement. METHODS: The multicenter Venogram Versus Intravascular Ultrasound for Diagnosing and Treating Iliofemoral Vein Obstruction (VIDIO) trial prospectively enrolled 100 symptomatic patients (Clinical Etiologic Anatomic Pathophysiologic [CEAP] classification of 4-6) with suspected iliofemoral venous outflow disease. Venous stenting for presumed significant iliofemoral vein stenosis, based on imaging and clinical findings, was performed on 68 patients. Based on imaging, stenosis was characterized as nonthrombotic in 48 patients and post-thrombotic in 20 patients. Each underwent baseline and poststenting venography and IVUS to compare the diagnostic and clinical usefulness of the tests. The revised Venous Clinical Severity Score was used to assess clinical patient outcome. A >4-point reduction in the revised Venous Clinical Severity Score between baseline and 6 months was used as an indicator of clinically meaningful improvement. Receiver operating characteristic curve analysis was used to determine the optimal diameter and area thresholds for prediction of clinical improvement. RESULTS: Clinical improvement after stenting was best predicted by IVUS baseline measurement of area stenosis (area under the curve, 0.64; P = .04), with >54% estimated as the optimal threshold of stenosis indicating interventional treatment. With measurement of lumen gain from baseline to after the procedure, the optimal reduction in vein stenosis correlative of later clinical improvement was >41%; IVUS measurement of area stenosis was most predictive (area under the curve, 0.70; P = .004). Venographic measurements of baseline stenosis and stenotic change were not predictive of later improvement. In a 48-patient nonthrombotic subset analysis, IVUS diameter rather than area measurements of baseline stenosis were significantly predictive of clinical success, but indicated a higher optimal threshold of stenosis (>61%) may be necessary. CONCLUSIONS: This study suggests that IVUS shows significant usefulness at predicting when stenting iliofemoral vein stenosis in patients clinical-etiologic-anatomic-pathophysiologic classification of 4-6 will result in significant symptom improvement. Our findings corroborate the conventional >50% cross-sectional area threshold by IVUS as defining a clinically significant iliofemoral stenosis that, when stented, has significant predictive value for symptom improvement. In nonthrombotic patients, however, a threshold of >61% diameter stenosis by IVUS may better predict clinical improvement.

Randomized double-blinded study comparing medical treatment versus iliac vein stenting in chronic venous disease.

OBJECTIVE: Iliac vein stenting has emerged as the procedure of choice in the treatment of iliac vein obstruction (IVO). However, clinical outcomes have never been studied by a randomized clinical trial. Our purpose was to compare medical and endovascular treatment results in symptomatic chronic venous disease (CVD) patients with significant IVO documented by intravascular ultrasound (IVUS). METHODS: Patients with Clinical, Etiology, Anatomy, and Pathophysiology clinical class C3 to C6 and a visual analog scale for pain (VAS pain) score >3 were considered eligible. We randomly assigned limbs with ≥50% IVO on IVUS to undergo medical treatment alone or medical treatment plus iliac vein stenting. The patient and clinical physician were blinded. Primary outcomes included change from baseline in VAS pain score, Venous Clinical Severity Score, and 36-Item Short Form Health Survey quality of life questionnaire. Secondary outcomes included stent integrity, migration, and patency rates at 6 months. RESULTS: Of 207 CVD patients, 58 (28%) were eligible and eight (14%) were excluded; 51 of 85 class C3 to C6 limbs (60%) had ≥50% IVO by IVUS. Iliac vein stenting, in randomized patients, was 100% technically successful. At 6 months' follow-up, the mean VAS pain score declined from a median of 8 to 2.5 in patients receiving stents and from 8 to 7 in patients receiving only medical treatment (P < .001). The Venous Clinical Severity Score dropped from a median of 18.5 to 11 after stenting and from 15 to 14 with medical treatment (P < .001). The 36-Item Short Form Health Survey (0-100) improved from a total median score of 53.9 to 85.0 with stenting and 48.3 to 59.8 after medical treatment (P < .001). There was no stent fracture or migration, and the primary, assisted primary, and secondary patency rates were 92%, 96%, and 100%, respectively (median, 11.8; range, 6-18 months). CONCLUSIONS: Endovascular treatment of IVO with stenting is safe and promotes effective relief of symptoms and improvement in quality of life compared with medical treatment alone in symptomatic CVD patients. Our results echo those achieved in numerous previously published nonrandomized clinical series.

Correlation between venous pressure gradients and intravascular ultrasound in the diagnosis of iliac vein compression syndrome.

OBJECTIVE: The objective of this study was to evaluate the correlation between venous pressure gradients (VPGs) and intravascular ultrasound (IVUS) for the diagnosis of caval-iliac venous obstructions in patients with advanced chronic venous insufficiency. METHODS: Fifty patients with advanced chronic venous insufficiency symptoms (Clinical, Etiology, Anatomy, and Pathophysiology class 3 to 6) were prospectively submitted to multiplanar venography (MV) with intravenous pressure measurements and IVUS. The patients' lower limbs were divided accordingly: group I, limbs with <50% obstruction on IVUS (n = 49); and group II, limbs with ≥50% obstruction on IVUS (n = 51). Receiver operating characteristic curves compared the diagnostic performance of the VPGs. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy assessed the performance of VPGs in categories to determine the presence of significant obstruction. Logistic regression assessed the capacity of the VPGs to identify significant obstruction. RESULTS: The most frequent point of venous compression according to IVUS was the proximal left common iliac vein (70%; P < .05). Group II showed a greater prevalence of transpelvic (group I, 8.2%; group II, 74.5%; P < .001) and paravertebral collaterals (group I, 4.1%; group II, 45.1%; P < .001) on MV. The femoral vein pressures at rest and after reactive hyperemia as well as the femorocaval gradient after reactive hyperemia (FCG-rh) and the femoral gradient after reactive hyperemia were significantly higher in group II (P = .001, P < .001, P = .002, and P = .006). The FCG-rh and the femoral gradient after reactive hyperemia presented the best diagnostic performance among the VPGs (P = .004 and P = .007) in the receiver operating characteristic curve analysis, although no significant differences between them were found. All the gradients presented low values of sensitivity (<40%), negative predictive value (<60%), and accuracy (<30%). Logistic regression showed that FCG-rh was significantly independent of MV (OR, 8.1; P = .011) in identifying significant obstructions. CONCLUSIONS: There is correlation between the VPGs and significant obstructions with IVUS. However, this correlation does not translate to a good diagnostic performance of these VPGs. Only the FCG-rh added significant information to MV in identifying significant caval-iliac vein obstructions.

Prospective, double-blind, randomized controlled trial comparing electrocoagulation and radiofrequency in the treatment of patients with great saphenous vein insufficiency and lower limb varicose veins.

OBJECTIVE: Thermoablation has been replacing conventional surgery in the surgical treatment of great saphenous vein (GSV) reflux in patients with lower limb varicose veins; however, thermoablation is expensive. Intravenous electrocoagulation (EC) may, selectively and safely, cause necrosis of the GSV wall, but the clinical results have never been studied. The objective of this study was to compare EC and radiofrequency ablation (RFA) in the treatment of GSV insufficiency, considering efficacy, complications, and effect on quality of life. METHODS: This was a prospective, double-blind, randomized clinical trial. Patients with lower limb varicose veins and GSV reflux confirmed by duplex ultrasound were randomized into two treatment groups: EC and RFA. Patients were followed up at 1 week, 3 months, and 6 months after the procedure. Occlusion of the GSV confirmed by duplex ultrasound was considered the primary outcome, and the rate of complications and improvement in quality of life, using the Aberdeen Varicose Vein Questionnaire score, were the secondary outcomes. RESULTS: Fifty-seven patients were included, with a total of 85 treated GSVs; 43 were treated with RFA and 42 with EC. There was no statistically significant difference between the groups regarding age (P = .264), sex (P = .612), Aberdeen Varicose Vein Questionnaire score (P = .054), and diameter (P = .880) and depth (P = .763) of the treated GSV. In the intraoperative period, immediately after thermoablation, all GSVs treated with EC presented no flow and incompressibility in the treated segment, whereas 12 limbs still had flow in the treated GSV (P < .001) and 9 veins showed compressibility (P < .001) when treated with RFA. The main postoperative complication was paresthesia; however, there was no statistical significance between the groups (P = .320) regarding its presence. Time to return to routine activities was lower in the EC group than in the RFA group (P = .026). There was no difference between the groups at the 3-month (P = .157) and 6-month (P = .157) follow-up in occlusion of the GSV and improvement of the quality of life score (P = .786 and P = .401, respectively). CONCLUSIONS: EC has been shown to be an effective method for ablation of the GSV, with venous occlusion rate, occurrence of complications, and effect on quality of life similar to those with RFA.

May-Thurner: diagnosis and endovascular management.

Common left iliac vein compression, otherwise known as May-Thurner (MT), is an anatomical risk factor for lower extremity deep vein thrombosis (DVT). MT refers to chronic compression of the left iliac vein against the lumbar spine by the overlying right common iliac artery. The compression may be asymptomatic. The syndrome is a clinical spectrum of physical findings and history plus the lesion. It is characterized by the varying degrees of venous hypertension. This can be non-thrombotic, combined with acute DVT or post-thrombotic. Traditionally, acute DVT was treated with standard anticoagulation and sometimes, thrombectomy. However these measures do not address the underlying culprit lesion of mechanical compression. Furthermore, if managed only with anticoagulation, patients with residual thrombus are at risk for developing recurrent DVT or post-thrombotic syndrome (PTS). Both retrospective and prospective studies have shown that endovascular management should be the preferred approach to dissolve proximal thrombus and to also treat the underlying compression with endovascular stent placement.

Criteria for detecting significant chronic iliac venous obstructions with duplex ultrasound.

OBJECTIVE: The purpose of this study was to determine the sonographic criteria for diagnosis of iliac venous outflow obstruction by assessing the correlation of this method with intravascular ultrasound (IVUS) in patients with advanced chronic venous insufficiency (CVI). METHODS: The evaluation included 15 patients (30 limbs; age, 49.4 ± 10.7 years; 1 man) with initial CVI symptoms (Clinical class, Etiology, Anatomy, and Pathophysiology [CEAP] classification, CEAP1-2) in group I (GI) and 51 patients (102 limbs; age, 50.53 ± 14.5 years; 6 men) with advanced CVI symptoms (CEAP3-6) in group II (GII). Patients from both groups were matched by gender, age, and race. The Venous Clinical Severity Score was considered. All patients underwent structured interviews and duplex ultrasound (DU) examination, measuring the flow phasicity, the femoral volume flows and velocities, and the velocity and obstruction ratios in the iliac vein. The reflux multisegment score was analyzed in both groups. Three independent observers evaluated individuals in GI. GII patients were submitted to IVUS, in which the area of the impaired venous segments was obtained and compared with the DU results and then grouped into three categories: obstructions <50%, obstructions between 50% and 79%, and obstructions ≥80%. RESULTS: The predominant clinical severity CEAP class was C1 in 24 of 30 limbs (80%) in GI and C3 in 54 of 102 limbs (52.9%) in GII. Reflux was severe (reflux multisegment score ≥3) in 3 of 30 limbs (10%) in GI and in 45 of 102 limbs (44.1%) in GII (P < .001). There was a moderately high agreement between DU and IVUS findings when they were grouped into three categories (κ = 0.598; P < .001) and high agreement when they were grouped into two categories (obstructions <50% and ≥50%; κ = 0.784; P < .001). The best cutoff points and their correlation with IVUS were 0.9 for the velocity index (r = -0.634; P < .001), 0.7 for the flow index (r = -0.623; P < .001), 0.5 for the obstruction ratio (r = 0.750; P < .001), and 2.5 for the velocity ratio (r = 0.790; P < .001). Absence of flow phasicity was observed in 62.5% of patients with obstructions ≥80%. An ultrasound algorithm was created using the measures and the described cutoff points with accuracy of 86.7% for detecting significant obstructions (≥50%) with high agreement (κ = 0.73; P < .001). CONCLUSIONS: DU presented high agreement with IVUS for detection of obstructions ≥50%. The velocity ratio in obstructions ≥2.5 is the best criterion for detection of significant venous outflow obstructions in iliac veins.