The impact of a male or female thrombotic family history on contraceptive counseling: a cohort study.

UNLABELLED: Essentials It is unknown if a male or female thrombotic family history influences risk in female relatives. We assessed thrombotic risk in female relatives of male and female patients with thrombosis. A hormonally related female thrombotic family history further increases risk in female relatives. This information could be important in counseling women on contraceptive options. Click to hear Prof. Rosendaal's perspective on venous thrombosis: etiology, pathogenesis, and prognosis SUMMARY: Background Women from thrombophilic families have increased risk of venous thromboembolism (VTE), which increases further during oral contraceptive (COC) use and pregnancy-postpartum. Whether this additional risk differs between relatives of male and female patients, or is different when that female patient had a hormonally related VTE (during COC use/pregnancy), is unknown. Methods One thousand five female relatives of consecutive patients with VTE from a family-based cohort were retrospectively followed for incident VTE from ages 15 to 50, first VTE, or study inclusion. Absolute and relative VTE risks adjusted for factors of patients (sex, age) and relatives (thrombophilia, COC use, pregnancy) were estimated in relatives of female and male patients and in relatives of female patients with and without hormonally related VTE. Results Absolute risk in relatives of female (0.32 [95% confidence interval [CI] 0.23-0.43]) vs. male patients (0.39 [95% CI 0.28-0.53]) was comparable. However, the heterogeneity analysis of risk estimates suggested that in relatives of female vs. male patients, the contribution of pregnancy-postpartum (hazard ratio [HR] 11.6 [95% CI 6.3-21.3] vs. HR6.6 [95% CI 2.8-15.2]) and, to a lesser extent, COC use (HR3.6 [95% CI 1.8-7.1] vs. HR2.7 [95% CI 1.5-5.0]) to the VTE risk differs. Absolute risk was significantly higher in relatives of female patients with hormonally related VTE (0.43 [95% CI 0.3-0.6]) vs. relatives of female patients without hormonally related VTE (0.13 [95% CI 0.05-0.27]), HR3.28 [95% CI 1.5-7.9]). The higher contribution of pregnancy-postpartum and COC use to the VTE risk was mainly observed in relatives of patients with hormonally related VTE. Conclusions These findings suggest that a family history from a female patient, especially when VTE was hormonally related, may further increase VTE risk in her female relatives. This information could be important in counseling women on contraceptive options.

Comparison of idrabiotaparinux with vitamin K antagonists for prevention of thromboembolism in patients with atrial fibrillation: the Borealis-Atrial Fibrillation Study.

BACKGROUND: Idrabiotaparinux, a long-acting inhibitor of factor Xa, was shown to be effective in the treatment of patients with venous thromboembolism. OBJECTIVE: To assess non-inferiority for the efficacy of idrabiotaparinux versus warfarin in patients with atrial fibrillation (AF) at risk of stroke and systemic embolism. Bleeding was also assessed. METHODS: This randomized, double-blind trial enrolled patients with electrocardiogram-documented AF. Idrabiotaparinux was administered weekly via subcutaneous injection, and warfarin was administered daily with dose adjustment to maintain the international normalized ratio between 2.0 and 3.0. Each idrabiotaparinux injection was 3 mg for the first 7 weeks, followed by 2 mg thereafter, except in patients with a creatinine clearance of 30-50 mL min(-1) or aged ≥ 75 years. The patients received 1.5 mg after the first 7 weeks. The efficacy outcome was the composite of all fatal or non-fatal strokes and systemic embolism. The safety outcome was clinically relevant bleeding (major and clinically relevant non-major bleeding). RESULTS: The study was terminated prematurely by the sponsor for strategic/commercial, not scientific, reasons, with 39% of the planned number of patients included and an average duration of treatment of 240 days. Of the 1886 idrabiotaparinux recipients, 20 developed stroke or systemic embolism (1.5% per year), whereas this occurred in 22 of the 1887 warfarin patients (1.6% per year, hazard ratio 0.98, 95% confidence interval 0.49-1.66). The annual incidence of bleeding was 6.1% in the idrabiotaparinux and 10.0% in the warfarin group (hazard ratio 0.61, 95% confidence interval 0.46-0.81). CONCLUSION: If anything, despite its early termination, the idrabiotaparinux regimen studied suggested a comparable efficacy to dose-adjusted warfarin, with a lower bleeding risk.

Maternal smoking during pregnancy and childhood overweight and fat distribution: the KOALA Birth Cohort Study.

UNLABELLED: What is already known about this subject There is an association between maternal smoking during pregnancy and higher body mass index (BMI) and overweight in childhood. What this study adds The association between maternal smoking during pregnancy and childhood overweight develops with age, starting with a lower birth weight, followed by weight catch-up in the first year after birth, finally leading to overweight at school age. Children of mothers who had smoked during pregnancy had a higher risk of exceeding the 85th percentile of BMI, waist circumference and total skinfold thickness at school age. BACKGROUND: Maternal smoking during pregnancy is associated with childhood overweight, but the association with fat distribution is not clear. OBJECTIVE: To explore the longitudinal association between smoking during pregnancy and childhood overweight and fat distribution. METHODS: In the KOALA Birth Cohort Study, repeated questionnaires were administered to 2698 mother-child pairs, including questions on smoking at 14 and 34 weeks of pregnancy. Main outcomes were birth weight, weight gain in the first year, body mass index (BMI) z-scores and overweight (BMI ≥85th percentile) at 1, 2, 4-5 and 6-7 years (n = 1730) and waist circumference and four skinfold thicknesses measured at home visits at age 6-7 years in a subgroup (n = 418). We used multivariable linear and logistic regression, with generalized estimating equations (GEE) for repeated measurements. RESULTS: Maternal smoking was associated with lower birth weight, higher weight gain in the first year and increasing overweight after infancy (change with age P = 0.02 in the GEE). Maternal smoking vs. non-smoking during pregnancy was associated with a higher risk of the child exceeding the 85th percentile of BMI (adjusted odds ratio [aOR] 3.72; 95% CI 1.33-10.4), waist circumference (aOR 2.65; 95% CI 1.06-6.59) and sum of skinfold thicknesses (aOR 4.45; 95% CI 1.63-12.2) at the age of 6-7 years. CONCLUSIONS: Maternal smoking during pregnancy is associated with lower birth weight, weight catch-up and development of overweight into childhood.

Nutritional status in patients with chronic pancreatitis.

OBJECTIVE: Chronic pancreatitis (CP) patients have an increased risk of malnutrition. Information about nutritional status of CP outpatients is scarce, and simple, sensitive methods to identify patients at risk are lacking. This explorative cross-sectional study was performed to survey the nutritional status of CP outpatients. SUBJECTS: Fifty patients with chronic or recurrent acute pancreatitis (RAP) had a nutritional assessment performed. Scores on nutritional screening tools and a quality of life questionnaire were assessed. General observations and relations between parameters were described. RESULTS: Thirty-nine patients had CP and eleven patients had RAP. According to the nutritional screening tools, 28-50% of the patients had a moderate or high risk of malnutrition. All domains of the Short Form Health Survey were significantly lowered in CP patients (all P0.001) compared with the Dutch norm values. A considerable number of patients scored below the 5th percentile on anthropometric measures. Mini Nutritional Assessment could not identify all patients with very low anthropometric scores. Substantial weight loss was not a sensitive indicator for functional impairment. CONCLUSION: CP outpatients are at risk of malnutrition. Currently used screening methods (for example, weight loss) are likely to be not sensitive enough to identify all patients with impaired body composition and restricted function. Therefore, some patients with objective decline in nutritional status will remain unidentified. An extended nutritional assessment is recommendable in CP patients.

Postintervention duration of anticoagulation in venous surgery.

For a substantial proportion of patients with deep venous thrombosis (DVT), current treatment strategies are suboptimal and new treatment options are needed. Especially for the group of patients who are at the highest risk for post-thrombotic syndrome, new treatment modalities such as catheter-directed thrombolysis and additional stenting are being investigated. With current clinical studies addressing new technical options, the medical management of patients following these interventions deserves attention. The duration of anticoagulant treatment following surgical or radiological interventions for DVT seems not to be influenced by the presence of a venous stent. According to recent ACCP 2012 guidelines the anticoagulant management in patients who have had any method of thrombus removal performed, the same intensity and duration of anticoagulant therapy as in comparable patients who do not undergo thrombosis removal is recommended (Grade 1B). In the acute phase of thrombosis, irrespective of the technique and whether or not stenting is applied, immediate anticoagulation following the procedure is pertinent to reduce the risk of recurrent thrombosis and thrombus propagation. The long-term treatment duration after venous interventions therefore may be tailored based on common risk factors for recurrent thrombosis and the individual risk for bleeding. Selected thrombophilia factors, d-dimer assessment and residual venous thrombosis provide markers for recurrent DVT. Currently, vitamin K antagonists) provide the main anticoagulants for (prolonged) anticoagulation, while the new oral anticoagulants emerge as promising alternatives. In case prolonged anticoagulation after unprovoked DVT is not indicated, cardiovascular risk management is warranted because of an increased rate of arterial thrombotic events after DVT; aspirin may be indicated as secondary prevention against recurrent thrombosis (while providing primary prevention against arterial thrombosis).

Adherence to a Mediterranean dietary pattern in early life is associated with lower arterial stiffness in adulthood: the Amsterdam Growth and Health Longitudinal Study.

OBJECTIVES: To investigate whether adherence to a Mediterranean dietary pattern during adolescence and early adulthood affects arterial stiffness in adulthood, and the extent to which any such association may be attributed to a beneficial impact of this diet on cardiovascular disease risk factors such as blood pressure, central fatness and dyslipidaemia. SETTING: The Amsterdam Growth and Health Longitudinal Study. DESIGN AND SUBJECTS: We compared longitudinal levels of adherence to a Mediterranean dietary pattern (aMED score with range 0-9) during adolescence and adulthood (two to eight repeated measures obtained between the ages of 13 and 36) between individuals with different levels of arterial stiffness in adulthood. The study population included 373 (196 women) apparently healthy adults in whom properties of the carotid, brachial and femoral arteries were assessed using ultrasonography at 36 years of age. RESULTS: After adjustments for potential confounders, individuals with stiffer carotid arteries (defined on the basis of the most adverse tertile of, for instance, the distensibility coefficient) had lower aMED scores (-0.32, 95% CI -0.60; -0.06) and were less likely to have adhered to this dietary pattern (aMED score ≥5, odds ratio 0.69, 95% CI 0.50; -0.94) during the preceding 24 years compared with those with less stiff arteries. Differences in aMED scores were already present in adolescence and were only in part explained by the favourable associations between the Mediterranean dietary pattern and other cardiovascular disease risk factors (up to 26%), particularly mean blood pressure (up to 19%). CONCLUSIONS: Promoting the Mediterranean diet in adolescence and early adulthood may constitute an important means of preventing arterial stiffness in adulthood.

International clinical practice guidelines for the treatment and prophylaxis of venous thromboembolism in patients with cancer.

BACKGROUND: Guidelines addressing the management of venous thromboembolism (VTE) in cancer patients are heterogeneous and their implementation has been suboptimal worldwide. OBJECTIVES: To establish a common international consensus addressing practical, clinically relevant questions in this setting. METHODS: An international consensus working group of experts was set up to develop guidelines according to an evidence-based medicine approach, using the GRADE system. RESULTS: For the initial treatment of established VTE: low-molecular-weight heparin (LMWH) is recommended [1B]; fondaparinux and unfractionated heparin (UFH) can be also used [2D]; thrombolysis may only be considered on a case-by-case basis [Best clinical practice (Guidance)]; vena cava filters (VCF) may be considered if contraindication to anticoagulation or pulmonary embolism recurrence under optimal anticoagulation; periodic reassessment of contraindications to anticoagulation is recommended and anticoagulation should be resumed when safe; VCF are not recommended for primary VTE prophylaxis in cancer patients [Guidance]. For the early maintenance (10 days to 3 months) and long-term (beyond 3 months) treatment of established VTE, LMWH for a minimum of 3 months is preferred over vitamin K antagonists (VKA) [1A]; idraparinux is not recommended [2C]; after 3-6 months, LMWH or VKA continuation should be based on individual evaluation of the benefit-risk ratio, tolerability, patient preference and cancer activity [Guidance]. For the treatment of VTE recurrence in cancer patients under anticoagulation, three options can be considered: (i) switch from VKA to LMWH when treated with VKA; (ii) increase in LMWH dose when treated with LMWH, and (iii) VCF insertion [Guidance]. For the prophylaxis of postoperative VTE in surgical cancer patients, use of LMWH o.d. or low dose of UFH t.i.d. is recommended; pharmacological prophylaxis should be started 12-2 h preoperatively and continued for at least 7-10 days; there are no data allowing conclusion that one type of LMWH is superior to another [1A]; there is no evidence to support fondaparinux as an alternative to LMWH [2C]; use of the highest prophylactic dose of LMWH is recommended [1A]; extended prophylaxis (4 weeks) after major laparotomy may be indicated in cancer patients with a high risk of VTE and low risk of bleeding [2B]; the use of LMWH for VTE prevention in cancer patients undergoing laparoscopic surgery may be recommended as for laparotomy [Guidance]; mechanical methods are not recommended as monotherapy except when pharmacological methods are contraindicated [2C]. For the prophylaxis of VTE in hospitalized medical patients with cancer and reduced mobility, we recommend prophylaxis with LMWH, UFH or fondaparinux [1B]; for children and adults with acute lymphocytic leukemia treated with l-asparaginase, depending on local policy and patient characteristics, prophylaxis may be considered in some patients [Guidance]; in patients receiving chemotherapy, prophylaxis is not recommended routinely [1B]; primary pharmacological prophylaxis of VTE may be indicated in patients with locally advanced or metastatic pancreatic [1B] or lung [2B] cancer treated with chemotherapy and having a low risk of bleeding; in patients treated with thalidomide or lenalidomide combined with steroids and/or chemotherapy, VTE prophylaxis is recommended; in this setting, VKA at low or therapeutic doses, LMWH at prophylactic doses and low-dose aspirin have shown similar effects; however, the efficacy of these regimens remains unclear [2C]. Special situations include brain tumors, severe renal failure (CrCl<30 mL min(-1) ), thrombocytopenia and pregnancy. Guidances are provided in these contexts. CONCLUSIONS: Dissemination and implementation of good clinical practice for the management of VTE, the second cause of death in cancer patients, is a major public health priority.

International clinical practice guidelines for the treatment and prophylaxis of thrombosis associated with central venous catheters in patients with cancer.

BACKGROUND: Although long-term indwelling central venous catheters (CVCs) may lead to pulmonary embolism (PE) and loss of the CVC, there is lack of consensus on management of CVC-related thrombosis (CRT) in cancer patients and heterogeneity in clinical practices worldwide. OBJECTIVES: To establish common international Good Clinical Practices Guidelines (GCPG) for the management of CRT in cancer patients. METHODS: An international working group of experts was set up to develop GCPG according to an evidence-based medicine approach, using the GRADE system. RESULTS: For the treatment of established CRT in cancer patients, we found no prospective randomized studies, two non-randomized prospective studies and one retrospective study examining the efficacy and safety of low-molecular-weight heparin (LMWH) plus vitamin K antagonists (VKAs). One retrospective study evaluated the benefit of CVC removal and two small retrospective studies were on thrombolytic drugs. For the treatment of symptomatic CRT, anticoagulant treatment (AC) is recommended for a minimum of 3 months; in this setting, LMWHs are suggested. VKAs can also be used, in the absence of direct comparisons of these two types of anticoagulants in this setting [Guidance]. The CVC can be kept in place if it is functional, well-positioned and non-infected and there is good resolution under close surveillance; whether the CVC is kept or removed, no standard approach in terms of AC duration has been established [Guidance]. For the prophylaxis of CRT in cancer patients, we found six randomized studies investigating the efficacy and safety of VKA vs. placebo or no treatment, one on the efficacy and safety of unfractionnated heparin, six on the value of LMWH, one double-blind randomized and one non randomized study on thrombolytic drugs and six meta-analyses of AC and CVC thromboprophylaxis. Type of catheter (open-ended like the Hickman(®) catheter vs. closed-ended catheter with a valve like the Groshong(®) catheter), its position (above, below or at the junction of the superior vena cava and the right atrium) and method of placement may influence the onset of CRT on the basis of six retrospective trials, four prospective non-randomized trials, three randomized trials and one meta-analysis. In light of these data: use of AC for routine prophylaxis of CRT is not recommended [1A]; a CVC should be inserted on the right side, in the jugular vein, and distal extremity of the CVC should be located at the junction of the superior vena cava and the right atrium [1A]. CONCLUSION: Dissemination and implementation of these international GCPG for the prevention and treatment of CRT in cancer patients at each national level is a major public health priority, needing worldwide collaboration.

Limitations of screening for occult cancer in patients with idiopathic venous thromboembolism.

BACKGROUND: Idiopathic venous thrombosis (IVT) is associated with occult malignancy in 10% of patients. The Trousseau study investigated whether extensive screening using abdominal and chest computed tomography (CT) scans and mammography in women would decrease mortality, compared with limited screening. Here, the costs and test characteristics of these screening strategies are presented, including true- and false-positive findings, sensitivity and specificity. METHODS: All investigations performed because of a suspicion of malignancy in the limited or extensive screening groups were collected. Costs were calculated using Dutch healthcare tariffs. RESULTS: A total of 342 and 288 patients with IVT were included in the extensive and the limited screening group, respectively. The prevalences of malignancy and mortality were comparable between these two groups, as were the abnormal findings during routine screening. In 30% of the extensively screened patients, the CT scans or mammography showed abnormalities necessitating further diagnostic work-up; this yielded six malignancies and resulted in a positive predictive value of 6.6%, sensitivity of 33% and specificity of 70%. Mean costs per patient were €165.17 for the routine and €530.92 for the extensive screening. CONCLUSION: Screening using CT scans and mammography results in extra costs due to the high percentage of false-positive findings for which a further diagnostic work-up is indicated.

Higher plasma high-mobility group box 1 levels are associated with incident cardiovascular disease and all-cause mortality in type 1 diabetes: a 12 year follow-up study.

AIMS/HYPOTHESIS: This study aimed to investigate the associations of plasma levels of the pro-inflammatory cytokine high-mobility group box 1 (HMGB1) with incident cardiovascular disease (CVD) and all-cause mortality in patients with type 1 diabetes. METHODS: We prospectively followed 165 individuals with diabetic nephropathy and 168 individuals with persistent normoalbuminuria who were free of CVD at study entry and in whom levels of HMGB1 and other cardiovascular risk factors were measured at baseline. RESULTS: During the course of follow-up (median, 12.3 years [interquartile range, 7.8-12.5]), 80 patients died, 82 suffered a fatal (n = 46) and/or non-fatal (n = 53) CVD event. After adjustment for age, sex, case-control status and other risk factors, patients with higher levels of log(e) HMGB1 had a higher incidence of fatal and non-fatal CVD and all-cause mortality: HR 1.55 (95% CI 0.94, 2.48) and HR 1.86 (95% CI 1.18, 2.93), respectively. Further adjustments for differences in markers of low-grade inflammation, endothelial and renal dysfunction and arterial stiffness did not attenuate these associations because plasma levels of HMGB1 were not independently associated with these variables. CONCLUSIONS/INTERPRETATION: In patients with type 1 diabetes, higher levels of plasma HMGB1 are independently associated with a higher risk of all-cause mortality and, to a lesser extent, with a higher incidence of CVD. Larger studies are needed to ascertain more definitely the role of HMGB1 in the development of vascular complications in diabetes.

Common alternative diagnoses in general practice when deep venous thrombosis is excluded.

BACKGROUND: In patients initially suspected of deep venous thrombosis (DVT) the diagnosis can be confirmed in approximately 10 to 30% of cases. For the majority of patients this means that eventually an alternative diagnosis is assigned. OBJECTIVE: To assess the frequency distribution of alternative diagnoses and subsequent management of patients in primary care after initial exclusion of DVT. In addition, assess the value of ultrasound examination for the allocation of alternative diagnoses. METHODS: Data were recorded by general practitioners alongside a diagnostic study in primary care in the Netherlands (AMUSE). Additional data were retrieved from a three-month follow-up questionnaire. A descriptive analysis was performed using these combined data. RESULTS: The most prevalent diagnoses were muscle rupture (18.5%), chronic venous insufficiency (CVI) (14.6%), erysipelas/cellulitis (12.6%) and superficial venous thrombosis (SVT) (10.9%). Alternative diagnoses were based mainly on physical examination; ultrasound examination (US) did not improve the diagnostic yield for the allocation of alternative diagnoses. In about 30% of all cases, a wait and see approach was used (27 to 41%). During the three-month follow-up nine patients were diagnosed with venous thromboembolic disease, three of which occurred in patients with the working diagnosis of SVT (p=0.026). CONCLUSIONS: We found that after exclusion of DVT in general practice a wait and see policy in the primary care setting is uneventful for almost one third of patients, but with the alternative diagnosis of SVT, patients may require closer surveillance since we found a significant association with thrombosis in these patients.

Early and mid-term results of a prospective observational study comparing emergency endovascular aneurysm repair with open surgery in both ruptured and unruptured acute abdominal aortic aneurysms.

The aim of the paper is to prospectively describe early and mid-term outcomes for emergency endovascular aneurysm repair (eEVAR) versus open surgery in acute abdominal aortic aneurysms (aAAAs), both unruptured (symptomatic) and ruptured. We enrolled all consecutive patients treated for aAAA at our center between April 2002 and April 2008. The main outcome parameters were 30-day, 6- and 12-month mortality (all-cause and aneurysm-related). Two hundred forty patients were enrolled in the study. In the unruptured aAAA group (n = 111), 47 (42%) underwent eEVAR. The 30-day, 6- and 12-month mortality rates were 6, 13 and 15% in the eEVAR group versus 11% (NS), 13% (NS) and 16% (NS) in the open group, respectively. In the ruptured aAAA group (n = 129), 25 (19%) underwent eEVAR (mortality rates: 20, 28 and 36%, respectively) compared with 104 (81%) patients who underwent open surgery (mortality rates: 45% (P = 0.021), 60% (P = 0.004) and 63% (P = 0.014), respectively). In conclusion, the present study showed a reduced 30-day, 6- and 12-month mortality of eEVAR compared with open surgery in all patients with aAAA, mainly due to a lower mortality in the ruptured aAAA group. Late aneurysm-related mortality occurred only in the eEVAR group.

Treatment for intermittent claudication and the effects on walking distance and quality of life.

The objective of the study was to provide an overview of the most common treatments for intermittent claudication and to determine the effectiveness in improving walking distance and quality of life based on a combination of direct and indirect evidence. We included trials that compared: angioplasty, surgery, exercise therapy or no treatment for intermittent claudication. Outcome measurements were walking distance (maximum, pain-free) and quality of life (physical, mental). We used a network meta-analysis model for the combination of direct and indirect evidence. We included 42 studies, presenting 3106 participants. The network meta-analysis showed that supervised exercise therapy (Δ = 1.62, P < 0.01), angioplasty (Δ = 1.89, P < 0.01) and surgery (Δ = 2.72, P = 0.02) increased walking distance significantly more than no treatment. Furthermore, supervised exercise therapy (Δ = 0.60, P < 0.01), angioplasty (Δ = 0.91, P = 0.01) and surgery (Δ = 1.07, P < 0.01) increased physical quality of life more than no treatment. However, in the sensitivity analysis, only supervised exercise therapy had additional value over no symptomatic treatment (Δ = 0.66, P < 0.01). In conclusion, this network meta-analysis indicates that supervised exercise therapy is more effective in both increasing walking distance and physical quality of life, compared with no treatment. Angioplasty and surgery also increase walking distance, compared with no treatment, but results for physical quality of life are less convincing.

Plasma levels of matrix metalloproteinase-9: a possible diagnostic marker of successful endovascular aneurysm repair.

OBJECTIVE: The aim of the study was evaluating the diagnostic value of plasma matrix metalloproteinase- (MMP)-2 and -9 and tissue inhibitor of MMP-1 (TIMP-1) for endoleak detection after endovascular aneurysm repair (EVAR). REPORT: Consecutive EVAR patients (n = 17) with endoleak and matched controls without endoleak (n = 20) were prospectively enrolled. Increased levels of MMP-9 were observed in patients with endoleak (P < 0.001). Regression analysis showed no significant influence of age, sex or abdominal aortic aneurysm (AAA) size. The receiver operating characteristic (ROC) curve of plasma MMP-9 levels showed that a cut-off value of 55.18 ng ml(-1) resulted in 100% sensitivity and 96% specificity with an AUC value of 0.988 (P < 0.001) to detect endoleak. CONCLUSIONS: Plasma MMP-9 levels appear to discriminate between patients with and without an endoleak with high sensitivity and specificity.

Feasibility of TEE-guided stroke risk assessment in atrial fibrillation-background, aims, design and baseline data of the TIARA pilot study.

BACKGROUND: Antithrombotic management in atrial fibrillation (AF) is currently based on clinical characteristics, despite evidence of potential fine-tuning with transoesophageal echocardiography (TEE). This open, randomised, multicentre study addresses the hypothesis that a comprehensive strategy of TEE-based aspirin treatment in AF patients is feasible and safe. METHODS: Between 2005 and 2009, ten large hospitals in the Netherlands enrolled AF patients with a moderate risk of stroke. Patients without thrombogenic TEE characteristics were randomised to aspirin or vitamin K antagonists (VKA). The primary objective is to show that TEE-based aspirin treatment is safe compared with VKA therapy. The secondary objective tests feasibility of TEE as a tool to detect echocardiographic features of high stroke risk. This report compares randomised to non-randomised patients and describes the feasibility of a TEE-based approach. RESULTS: In total, 310 patients were included. Sixty-nine patients were not randomised because of non-visualisation (n = 6) or TEE risk factors (n = 63). Compared with non-randomised patients, randomised patients (n = 241) were younger (65 ± 11 vs. 69 ± 9 years, p = 0.004), had less coronary artery disease (9 vs. 20%, p = 0.018), previous TIA (1.7 vs. 7.2%, p = 0.029), AF during TEE (25 vs. 54%, p < 0.001), mitral incompetence (55 vs. 70%, p = 0.038), VKA use (69 vs. 82%, p = 0.032), had a lower mean CHADS(2) score (1.2 ± 0.6 vs. 1.6 ± 1.0, p = 0.004), and left ventricular ejection fraction (59 ± 8 vs. 56 ± 8%, p = 0.016). CONCLUSIONS: This study shows that a TEE-based approach for fine-tuning stroke risk in AF patients with a moderate risk for stroke is feasible. Follow-up data will address the safety of this TEE-based approach.

Risk factors of arterial cardiovascular complications in patients with prior venous thromboembolism.

BACKGROUND: The effect of cardiovascular risk factors (CVRs) and thrombophilic defects on the risk of arterial cardiovascular complications in patients with prior venous thromboembolism (VTE) is unclear. OBJECTIVE: We investigated whether the risk of arterial cardiovascular complications is increased after VTE and whether CVRs and thrombophilic defects influence this risk. METHODS: Subjects were selected from three family cohorts of probands with VTE or arterial cardiovascular complication before the age of 50 and thrombophilic defects (i.e. hyperhomocysteinaemia, prothrombin G20210A or elevated FVIII). For this analysis, probands with arterial cardiovascular complications before inclusion and their relatives as well as relatives without the studied thrombophilic defects were excluded. We calculated the incidence of arterial cardiovascular complications (e.g. myocardial infarction, ischaemic stroke, transient ischaemic attack or peripheral arterial disease) in subjects with and without VTE and adjusted the relative risk for at least one CVR, two or more thrombophilic defects and quintiles of a propensity score (considering risk factors conditional to VTE history). RESULTS: 861 subjects were included, of whom 399 had experienced VTE before inclusion. Twelve arterial cardiovascular complications occurred in subjects with and nine in subjects without VTE history. Hence the annual incidence was 1.0 (95% CI 0.5 to 1.7) and 0.7 (0.3 to 1.2) in subjects with and without VTE (RR 1.5, 0.6 to 3.6). Adjusting for possible confounders did not change this relative risk. CONCLUSION: The mildly elevated risk of arterial cardiovascular complications in patients with prior VTE appears to be independent of cardiovascular risk factors and thrombophilic defects.

Statins Do Not Reduce Atrial Fibrillation After Cardiac Valvular Surgery: A Single Centre Observational Study.

INTRODUCTION: Statins may theoretically reduce postoperative atrial fibrillation (AF) in patients after cardiac valvular surgery due to preservation of endothelial function and anti-ischaemic, anti-inflammatory and anti-remodelling effects. METHODS: Two hundred seventy-two patients who underwent cardiac workup and subsequently cardiac valvular surgery without AF and concomitant coronary artery bypass grafting (CABG) at our hospital were selected. Preoperative drug use and postoperative AF were recorded. AF was defined as any episode of AF longer than 10 s. In addition, results from echocardiography and blood samples were retrieved. RESULTS: BASELINE CHARACTERISTICS WERE AS FOLLOWS: mean age was 65 ± 11 years, 142 (52%) patients were male, 189 (70%) had undergone aortic valve surgery and the mean left ventricular ejection fraction was 57 ± 12%. Statins were used by 79 patients (29%). Statin users, more often, had a prior percutaneous coronary intervention (25% vs 9%, p < 0.001) or CABG (24% vs 4%, p < 0.001), diabetes mellitus (22% vs 5%, p < 0.001) and more often used ß-blockers (51% vs 24%, p < 0.001). Patients in the non-statin group more often had surgery on more than one valve (10% vs 3%, p = 0.043) and had a higher cholesterol level (222 ± 48 vs 190 ± 43 mg/dl, p < 0.001). Postoperative AF occurred in 54% (43/79) of the patients with and in 55% (106/193) of the patients without statins (p = 0.941). There was also no difference in the timing of onset of AF or duration of hospital stay. CONCLUSION: In this observational study, statin use was not associated with a reduced incidence of AF in patients after cardiac valvular surgery.

EVAR suitability is not a predictor for early and midterm mortality after open ruptured AAA repair.

OBJECTIVE: The reported mortality reduction of emergency endovascular aneurysm repair (eEVAR) compared with open repair in patients with a ruptured abdominal aortic aneurysm (rAAA), as observed in observational studies, might be flawed by selection bias based on anatomical suitability for eEVAR. In the present study, we compared mortality in EVAR suitable versus non-EVAR-suitable patients with a ruptured AAA who were all treated with conventional open repair. MATERIALS AND METHODS: In all patients presenting with a suspected rAAA, computed tomography angiography (CTA) scanning was performed. All consecutive patients with a confirmed rAAA on preoperative CTA scan and treated with open repair between April 2002 and April 2008 were included. Anatomical suitability for eEVAR was determined by two blinded independent reviewers. Outcomes evaluated were mortality (intra-operative, 30-day, and 6-month), morbidity, complications requiring re-intervention and length of hospital stay. RESULTS: A total of 107 consecutive patients presented with a rAAA and underwent preoperative CTA scanning. In 25 patients, eEVAR was performed. In the 82 patients who underwent open repair, CTA showed an EVAR-suitable rAAA in 33 patients (41.8%) and a non-EVAR-suitable rAAA in 49 patients. Thirty-day and 6-month mortality rate was 15/33 (45.5%; 95% confidence interval (CI) 28.1-63.7) and 18/33 (54.5%; 95% CI 36.4-71.9) in the EVAR-suitable group versus 24/49 (49.0%; 95% CI 34.4-63.7) (P=0.75) and 29/49 (59.2%; 95% CI 44.2-73.0) (P=0.68) in the non-EVAR-suitable group, respectively. CONCLUSIONS: The present study suggests that anatomical suitability for EVAR is not associated with lower early and midterm mortality in patients treated with open ruptured AAA repair. Therefore, the reported reduction in mortality between eEVAR and open repair is unlikely due to selection bias based on anatomical AAA configuration.

Potential of integrated [18F] fluorodeoxyglucose positron-emission tomography/CT in identifying vulnerable carotid plaques.

BACKGROUND AND PURPOSE: There is a need for improved risk stratification of patients with TIA/stroke and carotid atherosclerosis. The purpose of this study was to prospectively investigate the potential of integrated (18)F-FDG PET/MDCT in identifying vulnerable carotid plaques. MATERIALS AND METHODS: Fifty patients with TIA/stroke with an ipsilateral carotid plaque causing <70% stenosis and a plaque on the contralateral asymptomatic side underwent integrated (18)F-FDG PET/MDCT within 36.1 ± 20.0 days (range, 9-95 days) of the last symptoms. Carotid plaque (18)F-FDG uptake was measured as both the mean and maximum blood-normalized SUV, known as the TBR. Using MDCT, we assessed volumes of vessel wall and individual plaque components. RESULTS: Mean TBR was only significantly larger in the ipsilateral plaques of patients who were imaged within 38 days (1.24 ± 0.04 [SE] versus 1.17 ± 0.05, P = .014). This also accounted for maximum TBR (1.53 ± 0.06 versus 1.42 ± 0.06, P = .015). MDCT-assessed vessel wall and LRNC volumes were larger in ipsilateral plaques of all patients (982.3 ± 121.3 versus 811.3 ± 106.6 mm(3), P = .016; 164.7 ± 26.1 versus 134.3 ± 35.2 mm(3), P = .026, respectively). CONCLUSIONS: In the present study, (18)F-FDG PET only detected significant differences between ipsilateral and contralateral asymptomatic plaques in patients with TIA/stroke who were imaged within 38 days, whereas MDCT detected larger vessel wall and LRNC volumes, regardless of time after symptoms. In view of the substantial overlap in measurements of both sides, it remains to be determined whether the differences we found will be clinically meaningful.

Thrombin generation in patients with a first acute myocardial infarction.

BACKGROUND: Despite improved treatment options, myocardial infarction is still an important cause of morbidity and mortality. One of the contributing mechanisms in the acute myocardial infarction (AMI) is plasma hypercoagulability. METHODS: We investigated hypercoagulability in 135 (first) patients with AMI using thrombin generation (TG) testing. TG testing was performed in plasmas, drawn upon admission and before medication administration, and subsequently after 4 days, 3 and 6 months. Further, we evaluated determinants of thrombin generation using multiple regression analysis of major coagulation proteins and inhibitors. Admission TG results were also related to 1-year outcome: cardiovascular death, recurrent myocardial infarction, a second coronary intervention [percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG)] and ischemic stroke. RESULTS: At day 0, the TG parameters peak height, endogenous thrombin potential (ETP) and lag time were increased compared with a reference population. Peak height and lag time stayed persistently increased in patients. The lowest half of the ETP values was statistically not significantly associated with an occurrence of endpoints. The lowest half of the ETP values combined with the upper half of the D-dimer values were associated with endpoints; odds ratio 5.8 (1.1-30.7). Tissue factor pathway inhibitor (TFPI) seems to be an important determinant of TG in AMI and healthy persons. CONCLUSIONS: TG reflects acute hypercoagulability during AMI and partly also in the 6-month period after the acute event. TG shows a trend of an inverse association with risk of recurrent ischemic cardiovascular complications. Unraveling mechanisms in TG might improve our understanding of the pathophysiology of AMI and direct future improvements in medical care.