Development and External Validation of a Prediction Model for Patients with Varicose Veins Suitable for Isolated Ambulatory Phlebectomy.

OBJECTIVE: Isolated ambulatory phlebectomy is a potential treatment option for patients with an incompetent great saphenous vein (GSV) or anterior accessory saphenous vein and one or more incompetent tributaries. Being able to determine which patients will most likely benefit from isolated phlebectomy is important. This study aimed to identify predictors for avoidance of secondary axial ablation after isolated phlebectomy and to develop and externally validate a multivariable model for predicting this outcome. METHODS: For model development, data from patients included in the SAPTAP trial were used. The investigated outcome was avoidance of ablation of the saphenous trunk one year after isolated ambulatory phlebectomy. Pre-defined candidate predictors were analysed with multivariable logistic regression. Predictors were selected using Akaike information criterion backward selection. Discriminative ability was assessed by the concordance index. Bootstrapping was used to correct regression coefficients, and the C index for overfitting. The model was externally validated using a population of 94 patients with an incompetent GSV and one or more incompetent tributaries who underwent isolated phlebectomy. RESULTS: For model development, 225 patients were used, of whom 167 (74.2%) did not undergo additional ablation of the saphenous trunk one year after isolated phlebectomy. The final model consisted of three predictors for avoidance of axial ablation: tributary length (< 15 cm vs. > 30 cm: odds ratio [OR] 0.09, 95% confidence interval [CI] 0.02 - 0.40; 15 - 30 cm vs. > 30 cm: OR 0.18, 95% CI 0.09 - 0.38); saphenofemoral junction (SFJ) reflux (absent vs. present: OR 2.53, 95% CI 0.81 - 7.87); and diameter of the saphenous trunk (per millimetre change: OR 0.63, 95% CI 0.41 - 0.96). The discriminative ability of the model was moderate (0.72 at internal validation; 0.73 at external validation). CONCLUSION: A model was developed for predicting avoidance of secondary ablation of the saphenous trunk one year after isolated ambulatory phlebectomy, which can be helpful in daily practice to determine the suitable treatment strategy in patients with an incompetent saphenous trunk and one or more incompetent tributaries. Patients having a longer tributary, smaller diameter saphenous trunk, and absence of terminal valve reflux in the SFJ are more likely to benefit from isolated phlebectomy.

[Spontaneous retroperitoneal hematoma]. / Spontaan retroperitoneaal hematoom.

Spontaneous retroperitoneal hematoma refers to bleeding of the retroperitoneal space without prior trauma or iatrogenic injury. Its diagnosis is often delayed due to a nonspecific clinical presentation. This case-series presents three patients with spontaneous retroperitoneal bleeding. Patient A presented with a spontaneous bleeding around the right iliopsoas muscle due to antiplatelet medication and was managed conservatively. Patient B had a spontaneous arterial bleeding near the right kidney, subsequently determined to be associated with a pheochromocytoma. Endovascular treatment successfully stopped the bleeding. The pheochromocytoma was resected during follow-up. Patient C had a spontaneous rupture of the left iliac vein with a concomitant deep vein thrombosis. She underwent emergent laparotomy, but unfortunately did not survive. This case-series emphasize the diverse presentation, varied causes, and different treatment strategies for spontaneous retroperitoneal hematoma. Timely diagnosis is hard, but crucial to enable an individualized treatment.

Quality of Life After Early Clot Removal for Acute Iliofemoral Deep Vein Thrombosis.

Objective: To evaluate patient reported outcome measures after early clot removal for acute deep vein thrombosis (DVT), using the Chronic Venous Disease Quality of Life Questionnaire (CIVIQ-20) and the Short Form Health Survey (SF-36). Methods: Cross sectional design. Patients who underwent early clot removal between June 2012 and November 2021 were asked to complete the two questionnaires once. Lower CIVIQ-20 and higher SF-36 scores indicate better quality of life (QoL). Primary endpoints were the median scores. The one sample Wilcoxon signed rank test was used to compare SF-36 physical and mental component summary (PCS and MCS) to the normative and CIVIQ-20 to the minimum. Secondary, non-parametric independent t test or Fisher's exact test examined how age, sex, body mass index, stent placement, re-intervention, and time of questionnaire completion related to QoL. Multivariable linear regression tested whether various variables were associated with QoL. Results: The response rate was 73.5% (n = 39). Median time of questionnaire completion was 1.8 years (interquartile range [IQR] 3.1) after clot removal. The median CIVIQ-20 of 29.0 (IQR 28.0) was slightly higher than the minimum value 20.0 (p < .001). The median PCS (50.5, IQR 16.6) and median MCS (50.2, IQR 14.2) did not differ from the normative of 50.0. However, wide IQRs indicated impairments for a subgroup of patients. None of the tested variables affected QoL except for the finding that re-interventions had a significantly negative impact on the SF-36 MCS (standardised ß coefficient of -0.4, p = .030). Conclusion: Overall patient reported outcome measures were satisfactory after early clot removal, but impaired physical and mental functioning levels were present in a subgroup of patients. Re-interventions were found to have a negative impact on mental QoL. This finding was independent of time that had passed between the procedure and questionnaire completion. This study emphasises that mental functioning deserves attention, besides the widely recognised physical consequences after invasive acute iliofemoral DVT treatment.

The background and role of catheter-directed thrombolysis evolving procedures for acute iliofemoral deep venous thrombosis.

Minimal invasive treatment such as early endovenous thrombus removal for iliofemoral deep venous thrombosis (DVT) emerged in the end of last century. The principle is catheter-directed thrombolysis (CDT) using either plasminogen activating agents alone, as ultrasound-assisted CDT, or in combination with mechanical devices as pharmaco-mechanical CDT. The interest for this treatment modality is the high rate of post-thrombotic syndrome (PTS) with anticoagulation (AC) alone, especially after iliofemoral DVT. Recently published randomized controlled trials (RCTs) comparing early thrombus removal with AC alone, as well as non-randomized studies, have demonstrated favorable rates, or at least a decrease of moderate and severe PTS, in favor of these procedures. This article will summarize the background and evolution of the procedures in the last three decades and discuss fundamental criteria for inclusion and exclusion, focusing on the procedures regarding thrombus age and location, technical issues, complications and results including different outcome measures for PTS, for which iliac DVT involvement is a massive risk factor to be prevented.

Quality of Life after Venous Stenting for Post-thrombotic Syndrome and the Effect of Inflow Disease.

OBJECTIVE: Patients with PTS experience an impaired quality of life (QoL). We aimed to study QoL in patients stented for post thrombotic syndrome (PTS) and analyze the influence of different parameters. METHODS: Patients stented for PTS after iliofemoral deep vein thrombosis were asked to complete the Chronic Venous Disease Quality of Life Questionnaire (CIVIQ-20) and the Short Form Health Survey (SF-36) in this cross-sectional study. All other data were collected retrospectively. Primary endpoints were median CIVIQ-20 and physical (PCS) and mental (MCS) component summary SF-36 scores. The influence of age, sex, and years between the procedure and completion of questionnaire were investigated using a multivariate linear regression model. Wilcoxon signed rank test compared the PCS and MCS with the normative. Effects of inflow from the deep femoral vein (DFV) and/or the femoral vein (FV) on QoL was analyzed in patients with patent stents. RESULTS: The response rate was 70.3% (n = 45/64). Time period (median) from stenting to questionnaire completion was 6.6 years (IQR: 8.0). Most stents were placed unilateral left-sided (73.3%). For patients with patent stents (n = 42) median CIVIQ-20 was 35.5 (IQR: 17.3), higher than the minimum of 20.0 (P < .001). Median PCS of 44.7 (IQR: 14.2) was lower (P < .001), and MCS of 55.9 (IQR: 7.1) higher (P = .001) than the normative (50.0). Time since stenting and sex were not associated with QoL. Age was a significant predictor [standardized coefficient ß = .36, P = .04] for QoL using the CIVIQ-20, but not for the SF-36. Inflow disease did not impact QoL, but patients with occluded stents (n = 3) had poor functioning levels. CONCLUSION: Quality of life is impaired after venous stenting for PTS, particularly physical functioning, among patients with an open stent, but was similar between patients with good and impaired inflow. Patients with a permanent stent occlusion had the lowest QoL.

Long Term Follow Up, Causes for Re-intervention, and Consequences for Surveillance After Stenting for Proximal Deep Vein Obstruction.

OBJECTIVE: Venous stenting is performed increasingly for acute deep vein thrombosis (DVT) and post-thrombotic syndrome (PTS) with good short term patency results, but long term data are scarce. The purpose of this study was to evaluate long term outcome of stenting for acute DVT and PTS and to study causes of re-intervention. METHODS: All patients stented for acute DVT and PTS between May 2006 and November 2021 were included retrospectively in this single centre cohort study. Patency was studied by duplex ultrasound (DUS) or computed tomography. The primary endpoint was stent patency. Re-intervention free survival was calculated using Kaplan-Meier methods. Secondary endpoints were causes of re-intervention, using the Pouncey classification system (2022). Binary logistic regression was used to calculate odds ratios for predictors of re-intervention. RESULTS: A total of 114 patients were included, with 129 limbs involved (acute DVT n = 53; 41%), PTS n = 76; 59%). Median follow up was 2.3 years (interquartile range [IQR] 2.3) for acute DVT and 5.2 years (IQR 7.1) for PTS. Primary patency, secondary patency, and permanent occlusion were 73.5%, 98.1%, and 1.9% for acute DVT, and 63.2%, 92.1%, and 7.9% for PTS limbs. Overall, 41 limbs underwent at least one re-intervention: 14 in the acute DVT group and 27 for PTS. Most re-interventions (82.9%) were performed within the first year after stenting. Missed inflow, insufficient flow, and thrombosis despite anticoagulation were the most common causes of re-intervention. The strongest predictor for re-intervention for PTS was inflow disease (odds ratio 3.57, 95% confidence interval 1.26 - 10.13, p= .017). CONCLUSION: Long term patency of deep venous stenting is good. Re-interventions are typically performed in the first year and are potentially preventable by improving the procedure and patient selection. Since secondary patency rates are excellent, selected patients may be considered for discharge from long term surveillance.

A Case of Complete Resolution of Cauda Equina Syndrome Caused by Extensive Iliocaval Thrombosis: The Role of Thrombolysis and Venous Stents.

PURPOSE: The cauda equina syndrome (CES) is a rare condition affecting less than 1 in 100,000 patients annually. Diagnosing CES is challenging because of its rare incidence, potentially subtle presentation, and various underlying etiologies. Vascular causes, such as inferior vena cava (IVC) thrombosis, are uncommon but should be considered, since timely recognition and treatment of deep vein thrombosis (DVT) as a cause of CES can avoid irreversible neurological damage. CASE REPORT: A 30-year-old male presented with partial CES caused by nerve root compression due to venous congestion from an extensive iliocaval DVT. He completely recovered after thrombolysis and stenting of the IVC. His iliocaval tract remained patent until the last date of follow-up at 1 year without signs of post-thrombotic syndrome. Broad molecular, infectious, and hematological laboratory tests did not reveal any underlying disease for the thrombotic event, particularly no hereditary or acquired thrombophilia. CONCLUSION: Timely recognition of venous thrombosis as a cause of CES is essential. This is the first case report of CES caused by an extensive iliocaval DVT successfully treated with thrombolysis and venous stenting with good resolution of DVT and CES. CLINICAL IMPACT: This case-report describes a patient with cauda equina syndrome resulting from an extensive iliocaval deep vein thrombosis due to an underlying stenosis of the inferior vena cava. Thrombolysis and venous stenting succesfully restored venous patency and thereby relieved symptoms and signs of cauda equina syndrome, in addition to (long-term) therapeutic dose anticoagulation. It is important to timely recognize deep vein thrombosis as a cause of cauda equina syndrome and to consider endovenous treatment in a specialized center.

Spontaneous Iliac Vein Ruptures: A Systematic Review.

INTRODUCTION: Spontaneous iliac vein rupture is a rare, but frequently lethal condition. It is important to timely recognize its clinical features and immediately start adequate treatment. We aimed to increase awareness to clinical features, specific diagnostics, and treatment strategies of spontaneous iliac vein rupture by evaluating the current literature. METHODS: A systematic search was conducted in EMBASE, Ovid MEDLINE, Cochrane, Web of Science, and Google Scholar from inception until January 23, 2023, without any restrictions. Two reviewers independently screened for eligibility and selected studies describing a spontaneous iliac vein rupture. Patient characteristics, clinical features, diagnostics, treatment strategies, and survival outcomes were collected from included studies. RESULTS: We included 76 cases (64 studies) from the literature, mostly presenting with left-sided spontaneous iliac vein rupture (96.1%). Patients were predominantly female (84.2%), had a mean age of 61 years, and frequently presented with a concomitant deep vein thrombosis (DVT) (84.2%). After various follow-up times, 77.6% of the patients survived, either after conservative, endovascular, or open treatment. Endovenous or hybrid procedures were frequently performed if the diagnose was made before treatment, and almost all survived. Open treatment was common if the venous rupture was missed, for some cases leading to death. CONCLUSION: Spontaneous iliac vein rupture is rare and easily missed. The diagnose should at least be considered for middle-aged and elderly females presenting with hemorrhagic shock and concomitant left-sided DVT. There are various treatment strategies for spontaneous iliac vein rupture. An early diagnose brings options for endovenous treatment, which seems to have good survival outcomes based on previously described cases.

Indication and outcome of lupus anticoagulant and antiphospholipid antibodies testing in routine clinical practice.

OBJECTIVES: Lupus anticoagulans (LACs) and aPLs, both further summarized as aPL, are frequently assessed in routine daily clinical practice in diagnostic workups for suspected autoimmune diseases or to test for underlying risk factors in patients with thrombosis or obstetric complications. The aim of this study was to determine the prevalence of aPL positivity in patients with an indication for aPL testing in routine clinical practice. METHODS: In this retrospective single-centre study, indication for aPL testing, aPL test results and clinical data were collected for patients tested between June 2015 and April 2018. RESULTS: During the study period, 16 847 single aPL tests were performed in 2139 patients. In 212 patients one or more positive aPL test was found, confirmed in 43.9% with a second positive test. Indications for aPL testing were diagnostic workup/follow-up of autoimmune diseases (33.6%), thrombosis (21.4%) and obstetric complications (28%). Seventy-four patients (3.5% of all patients) fulfilled the criteria of APS, of whom 51% were newly diagnosed. Second positive aPL titres and titres of APS patients were significantly higher compared with positive aPL titres at the first measurement (P < 0.05). Patients with indications of arterial thrombosis and diagnostic workup/follow-up of autoimmune diseases had significantly higher levels of aCL IgG and anti-ß2 glycoprotein I (ß2GPI) IgG compared with patients with other indications. CONCLUSION: The prevalence of one or more positive aPL test was 9.9% and APS was diagnosed in 3.5% of the patients. Patients with arterial thrombosis had significantly higher anti-ß2GPI IgG and aCL IgG, which should be confirmed in future studies.

Common genetic variation in the 3'-BCL11B gene desert is associated with carotid-femoral pulse wave velocity and excess cardiovascular disease risk: the AortaGen Consortium.

BACKGROUND: Carotid-femoral pulse wave velocity (CFPWV) is a heritable measure of aortic stiffness that is strongly associated with increased risk for major cardiovascular disease events. METHODS AND RESULTS: We conducted a meta-analysis of genome-wide association data in 9 community-based European ancestry cohorts consisting of 20 634 participants. Results were replicated in 2 additional European ancestry cohorts involving 5306 participants. Based on a preliminary analysis of 6 cohorts, we identified a locus on chromosome 14 in the 3'-BCL11B gene desert that is associated with CFPWV (rs7152623, minor allele frequency=0.42, ß=-0.075±0.012 SD/allele, P=2.8×10(-10); replication ß=-0.086±0.020 SD/allele, P=1.4×10(-6)). Combined results for rs7152623 from 11 cohorts gave ß=-0.076±0.010 SD/allele, P=3.1×10(-15). The association persisted when adjusted for mean arterial pressure (ß=-0.060±0.009 SD/allele, P=1.0×10(-11)). Results were consistent in younger (<55 years, 6 cohorts, n=13 914, ß=-0.081±0.014 SD/allele, P=2.3×10(-9)) and older (9 cohorts, n=12 026, ß=-0.061±0.014 SD/allele, P=9.4×10(-6)) participants. In separate meta-analyses, the locus was associated with increased risk for coronary artery disease (hazard ratio=1.05; confidence interval=1.02-1.08; P=0.0013) and heart failure (hazard ratio=1.10, CI=1.03-1.16, P=0.004). CONCLUSIONS: Common genetic variation in a locus in the BCL11B gene desert that is thought to harbor 1 or more gene enhancers is associated with higher CFPWV and increased risk for cardiovascular disease. Elucidation of the role this novel locus plays in aortic stiffness may facilitate development of therapeutic interventions that limit aortic stiffening and related cardiovascular disease events.

Incidence and prognosis of transient neurological attacks.

CONTEXT: Transient neurological attacks (TNAs) are attacks with temporary (<24 hours) neurological symptoms. These symptoms can be focal, nonfocal, or a mixture of both. The prognostic significance of TNAs with focal symptoms (better known as transient ischemic attacks [TIAs]) is well understood. Conversely, hardly anything is known about the prognostic significance of TNAs with nonfocal or mixed symptoms. OBJECTIVE: To study the incidence and prognosis of focal TNAs (or TIAs), nonfocal TNAs, and mixed TNAs. DESIGN, SETTING, AND PARTICIPANTS: The study population comprised 6062 community-dwelling Rotterdam Study participants who were aged 55 years or older and free from stroke, myocardial infarction, and dementia at baseline (1990-1993). They were followed up for events until January 1, 2005. We analyzed the associations between incident TNAs and subsequent adverse events with age- and sex-adjusted Cox regression models. MAIN OUTCOME MEASURES: Stroke, ischemic heart disease, or dementia. RESULTS: During 60 535 person-years, 548 participants developed TNA (282 focal, 228 nonfocal, and 38 mixed). The incidence rate per 1000 person-years was 4.7 (95% confidence interval [CI], 4.1-5.2) for focal TNA, 3.8 (95% CI, 3.3-4.3) for nonfocal TNA, and 0.6 (95% CI, 0.4-0.9) for mixed TNA. Participants with focal TNA were at higher risk of subsequent stroke than participants without TNA (n = 46 vs 540; hazard ratio [HR], 2.14; 95% confidence interval [CI]; 1.57-2.91) but had an equal risk of ischemic heart disease and dementia. Nonfocal TNA patients were at higher risk of stroke (27 vs 540; HR, 1.56; 95% CI, 1.08-2.28) and dementia (30 vs 552; HR, 1.59; 95% CI, 1.11-2.26) than participants without TNA. Mixed TNA patients were at higher risk of stroke (6 vs 540; HR, 2.48; 95% CI, 1.11-5.56), ischemic heart disease (8 vs 779; HR, 2.26; 95% CI, 1.07-4.78), vascular death (8 vs 594; HR, 2.54; 95% CI, 1.31-4.91), and dementia (7 vs 552; HR, 3.46; 95% CI, 1.72-6.98) than participants without TNA. CONCLUSION: Patients who experience nonfocal TNAs, and especially those with mixed TNAs, have a higher risk of major vascular diseases and dementia than persons without TNA.

Heritability of blood pressure traits and the genetic contribution to blood pressure variance explained by four blood-pressure-related genes.

OBJECTIVE: To study the heritability of four blood pressure traits and the proportion of variance explained by four blood-pressure-related genes. METHODS: All participants are members of an extended pedigree from a Dutch genetically isolated population. Heritability and genetic correlations of systolic blood pressure, diastolic blood pressure, mean arterial pressure and pulse pressure were assessed using a variance components approach (SOLAR). Polymorphisms of the alpha-adducin (ADD1), angiotensinogen (AGT), angiotensin II type 1 receptor (AT1R) and G protein beta3 (GNB3) genes were typed. RESULTS: Heritability estimates were significant for all four blood pressure traits, ranging between 0.24 and 0.37. Genetic correlations between systolic blood pressure, diastolic blood pressure and mean arterial pressure were high (0.93-0.98), and those between pulse pressure and diastolic blood pressure were low (0.05). The ADD1 polymorphism explained 0.3% of the variance of pulse pressure (P = 0.07), and the polymorphism of GNB3 explained 0.4% of the variance of systolic blood pressure (P = 0.02), 0.2% of mean arterial pressure (P = 0.05) and 0.3% of pulse pressure (P = 0.06). CONCLUSION: Genetic factors contribute to a substantial proportion of blood pressure variance. In this study, the effect of polymorphisms of ADD1, AGT, AT1R and GNB3 explained a very small proportion of the heritability of blood pressure traits. As new genes associated with blood pressure are localized in the future, their effect on blood pressure variance should be calculated.

Alpha-adducin polymorphism, atherosclerosis, and cardiovascular and cerebrovascular risk.

BACKGROUND AND PURPOSE: Carriers of the 460Trp allele of the alpha-adducin gene (ADD1) show higher rates of sodium reabsorption compared with homozygous carriers of the Gly460 allele and were found to have an increased risk of hypertension and cardiovascular disease. We studied the association between the Gly460Trp polymorphism and atherosclerosis, cardiovascular disease, and cerebrovascular disease. METHODS: Intima-media thickness of the common carotid artery, as well as incident stroke and myocardial infarction, were studied within 6471 subjects of the Rotterdam Study. Within 1018 subjects of the Rotterdam Scan Study, prevalent silent brain infarcts and cerebral white matter lesions were studied. Subjects were grouped into 460Trp carriers (variant carriers) and homozygous carriers of the Gly460 allele (reference). RESULTS: Intima-media thickness of the common carotid artery was 0.80 mm in variant carriers compared with 0.79 mm in the reference group (P=0.04). Variant carriers had an increased risk of any stroke (hazard ratio [HR], 1.22; 95% CI, 1.02 to 1.45), ischemic stroke (HR, 1.29; 95% CI, 1.02 to 1.63), hemorrhagic stroke (HR, 1.07; 95% CI, 0.59 to 1.92), and of myocardial infarction (HR, 1.33; 95% CI, 1.05 to 1.69). For any ischemic stroke, there was a significant interaction between the Gly460Trp polymorphism and hypertension. Variant carriers more often had a silent brain infarct (odds ratio, 1.36; 95% CI, 0.98 to 1.88) and had more subcortical white matter lesions than the reference group (1.45 vs1.24 mL; P=0.22). CONCLUSIONS: The Gly460Trp polymorphism is associated with atherosclerosis, cardiovascular disease, and cerebrovascular disease, especially in hypertensive subjects.