Search

Background: The association between heart rate (HR) and pulmonary embolism (PE) outcomes has not been well studied. Furthermore, optimal cutoffs to identify low-risk and intermediate- to high-risk patients are not well known. Research Question: Does an association exist between baseline HR and PE outcome across the continuum of HR values? Study Design and Methods: The current study included 44,331 consecutive nonhypotensive patients with symptomatic PE from the Registro Informatizado de la Enfermedad TromboEmbólica registry between 2001 and 2021. Outcomes included 30-day all-cause and PE-specific mortality. We used hierarchical logistic regression to assess the association between admission HR and outcomes. Results: A positive relationship was found between admission HR and 30-day all-cause and PE-related mortality. Considering an HR of 80 to 99 beats/min as a reference, patients in the higher HR strata showed higher rates of all-cause death (adjusted OR, 1.5 for HR of 100-109 beats/min; adjusted OR, 1.7 for HR of 110-119 beats/min; adjusted OR, 1.9 for HR of 120-139 beats/min; and adjusted OR, 2.4 for HR of ≥ 140 beats/min). Patients in the lower strata of HR showed significantly lower rates of 30-day all-cause mortality compared with the same reference group (adjusted OR, 0.6 for HR of 60-79 beats/min; and adjusted OR, 0.5 for HR of < 60 beats/min). The findings for 30-day PE-related mortality were similar. For identification of low-risk patients, a cutoff value of 80 beats/min (vs 110 beats/min) increased the sensitivity of the simplified Pulmonary Embolism Severity Index (sPESI) from 93.4% to 98.8%. For identification of intermediate- to high-risk patients, a cutoff value of 140 beats/min (vs 110 beats/min) increased the specificity of the Bova score from 93.2% to 98.0%. Interpretation: In nonhypotensive patients with acute symptomatic PE, a high HR portends an increased risk of all-cause and PE-related mortality. Modifying the HR cutoff in the sPESI and the Bova score improves prognostication of patients with PE.

COVID-19 infection causes respiratory pathology with severe interstitial pneumonia and extra-pulmonary complications; in particular, it may predispose to thromboembolic disease. The current guidelines recommend the use of thromboprophylaxis in patients with COVID-19, however, the optimal heparin dosage treatment is not well-established. We conducted a multicentre, Italian, retrospective, observational study on COVID-19 patients admitted to ordinary wards, to describe clinical characteristic of patients at admission, bleeding and thrombotic events occurring during hospital stay. The strategies used for thromboprophylaxis and its role on patient outcome were, also, described. 1091 patients hospitalized were included in the START-COVID-19 Register. During hospital stay, 769 (70.7%) patients were treated with antithrombotic drugs: low molecular weight heparin (the great majority enoxaparin), fondaparinux, or unfractioned heparin. These patients were more frequently affected by comorbidities, such as hypertension, atrial fibrillation, previous thromboembolism, neurological disease, and cancer with respect to patients who did not receive thromboprophylaxis. During hospital stay, 1.2% patients had a major bleeding event. All patients were treated with antithrombotic drugs; 5.4%, had venous thromboembolism [30.5% deep vein thrombosis (DVT), 66.1% pulmonary embolism (PE), and 3.4% patients had DVT + PE]. In our cohort the mortality rate was 18.3%. Heparin use was independently associated with survival in patients aged ≥ 59 years at multivariable analysis. We confirmed the high mortality rate of COVID-19 in hospitalized patients in ordinary wards. Treatment with antithrombotic drugs is significantly associated with a reduction of mortality rates especially in patients older than 59 years.

Fixed dose unfractionated or low molecular weight heparin is the recommended treatment for venous thromboembolism (VTE) prevention in hospitalized patients. However, its efficacy has been questioned in obese population. Results of previous studies on weight-adjusted doses of heparin for VTE prevention are contradictory. Different anticoagulant regimens are used in clinical practice, but their role remains to be elucidated.To clarify the efficacy and safety of weight-adjusted dose heparin for VTE prevention in obese subjects hospitalized for medical and surgical conditions.Twelve studies were identified as reporting VTE occurrence, major or minor bleeding and anti-Xa levels. A random-effect meta-analysis was conducted to derive odds ratios (OR) comparing fixed vs weight adjusted-doses heparins on VTE occurrence, bleeding, anti-Xa levels. Medical and surgical patients, prospective vs retrospective and quality of studies were extracted for moderators and meta-regression analysis.Weight-adjusted dose heparin administration was not associated with reduced VTE occurrence (6320/13317 patients, OR 1.03, 95% C.I. 0.79 to 1.35), nor increased bleeding (5840/10906 patients, OR 0.84, 95% C.I. 0.65 to 1.08), but it was associated with higher anti-Xa levels (284/294 patients, ES 2.04, 95% C.I. 1.16 to 2.92, p0.0001). A significant heterogeneity was present for comparison of anti-Xa levels (IWeight-adjusted dose as compared to fixed-dose of heparins in the prevention of VTE in obese patients was not associated with a lower risk of VTE nor a higher risk of bleeding.

Venous thromboembolism (VTE) is one of the leading cardiovascular etiologies of maternal morbidity and mortality. Indeed, pulmonary embolism (PE) accounts for approximately 9% of pregnancy-related deaths. In addition, pregnancy-related deep-vein thrombosis (DVT) can lead to (severe) post-thrombotic syndrome [...]

Background Coronavirus Disease 2019 (COVID-19) is responsible for a worldwide pandemic, with a high rate of morbidity and mortality. The increasing evidence of an associated relevant prothrombotic coagulopathy has resulted in an increasing use of antithrombotic doses higher than usual in COVID-19 patients. Information on the benefit/risk ratio of this approach is still lacking. Objective To assess the incidence of relevant bleeding complications in association with the antithrombotic strategy and its relationship with the amount of drug. Methods Consecutive COVID-19 patients admitted between February and April 2020 were included in a retrospective analysis. Major bleedings (MB) and clinically relevant non-major bleeding (CRNMB) were obtained from patient medical records and were adjudicated by an independent committee. Results Of the 324 patients who were recruited, 240 had been treated with prophylactic doses and 84 with higher doses of anticoagulants. The rate of the composite endpoint of MB or CRNMB was 6.9 per 100-person/months in patients who had been given prophylactic doses, and 26.4 per 100-person/months in those who had been prescribed higher doses (hazard ratio, 3.89; 95% confidence interval, 1.90-7.97). The corresponding rates for overall mortality were 12.2 and 20.1 per 100-person/months, respectively. Conclusions The rate of relevant bleeding events was high in patients treated with (sub)therapeutic doses of anticoagulants. In the latter group, overall mortality did not differ from that of patients treated with standard prophylactic doses and was even higher. Our result does not support a strategy of giving (sub)therapeutic doses of anticoagulants in non-critically ill patients with COVID-19.

Background An abnormal ankle-brachial pressure index (ABI) is a marker of the risk for increased total and cardiovascular (CV) mortality. However, it is not clear whether it is associated with an even worse prognosis in patients with previous CV events or with cancer mortality. Materials and Methods Consecutive subjects undergoing ABI assessment for suspected peripheral artery disease or for stratification of CV risk in ten centers in the Veneto Region (northeast Italy), between 2011 and 2014 were enrolled. The ABI was expressed as normal ≥0.9 to ≤1.3, and abnormal 1.3. All-cause mortality and CV or cancer mortality and hospitalizations for CV disease were collected from administrative databases up to December 2018. Results The study enrolled 1,177 patients. ABI was abnormal in 57.2%. Median follow-up was 61.6 months (53.4–70.1). All-cause, CV and cancer mortality were higher in patients with abnormal than normal ABI, with hazard ratios (HR) respectively 2.0 (95% CI 1.48–2.69), 1.98 (95% CI 1.24–3.17) and 1.85 (95% CI 1.09–3.15). Among subjects with abnormal ABI, the risk of overall mortality, HR 1.57 (95% CI 1.17–2.12), and CV mortality, HR 2.39 (95% CI 1.43–3.99), was higher in those with previous CV events. These latter also had a higher risk of hospitalization for myocardial infarction and stroke: HR 1.85 (95% CI 1.023.37) and 2.17 (95% CI 1.10–4.28). Conclusions The co-existence of abnormal ABI and a history of CV events identifies subjects at higher risk, who call for a more aggressive approach. Abnormal ABI is also a predictor of cancer mortality.

Background SARS-CoV2 infection are frequently associated with cardiovascular manifestations, in particular with symptomatic acute coronary syndromes, cardiac arrhythmias and acute heart failure. However, the elevation of serum troponin seems to be non specific, and a cardiologic diagnostic workup should be performed. We aimed to assess the clinical characteristic and the prevalence of left ventricular (LV) dyssynergy patterns in a cohort of hospitalized non-critically ill COVID-19 patientsMethods Consecutive patients with an objective diagnosis of COVID-19, from February to April 2020. Baseline characteristics and comorbidities was collected. In case of increased troponin levels or symptoms suggestive for a concomitant cardiac syndrome, patients undergo to serial electrocardiograms, serial Troponin tests and bedside transthoracic echocardiogram.Results 402 consecutive patients were enrolled: 55 patients underwent an echocardiographic exam because of an increase in troponin levels or a suspected myocardial injury. Segmental left ventricular abnormalities were found in 10 (median WMSI 2.03 IQR 1.38-2.75) with a median LV ejection fraction was 30.1 % IQR, median troponin level was 3083 ng/L, median BNP was 761 ng/L. Death for any cause occurred in 4 patients among patients with regional LV abnormalities and in 3 with normal regional function (p= 0,02).Discussion A single bedside transthoracic echocardiogram performed in non critically ill COVID-19 patients with suspected cardiac injury has the potential to better assist clinicians in their challenging decision process. As an isolated increase of troponin levels is common in COVID patients, a bed-side echocardiographic evaluation of cardiac function should be routinely implemented during their early evaluation.

Background: The choice of the imaging modality for diagnosis of pulmonary embolism (PE) could be influenced by provider, patient or hospital characteristics, or over time. However, little is known about the choice of the diagnostic modalities in practice. The aim of this study was to evaluate the variations in the use of imaging modalities for patients with acute PE. Methods: Using the data from Registro Informatizado Enfermedad TromboEmbolica (RIETE), a prospective international registry of patients with venous thromboembolism (March 2001–January 2019), we explored the imaging modalities used in patients with acute PE. The imaging modalities included computed tomography pulmonary angiography, ventilation/perfusion scanning, pulmonary angiography, a combination of these tests, or PE signs and symptoms plus imaging-confirmed proximal deep vein thrombosis but no chest imaging. Results: Among 38 025 patients with confirmed PE (53.1% female, age: 67.3±17 years), computed tomography pulmonary angiography was the dominant modality of diagnosis in all RIETE enrollees (78.2% [99% CI, 77.6–78.7]); including pregnant patients (58.9% [99% CI, 47.7%–69.4%]) and patients with severe renal insufficiency (62.5% [99% CI, 59.9–65.0]). A greater proportion of patients underwent ventilation/perfusion scanning in larger hospitals compared with smaller hospitals (13.1% versus 7.3%, P P Conclusions: In a large multinational PE registry, variations were observed in the use of imaging modalities according to patient or institutional factors and over time. However, computed tomography pulmonary angiography was the dominant modality of diagnosis, even in pregnancy and severe renal insufficiency. The safety, costs, and downstream effects of these tests on PE-related and non-PE-related outcomes warrant further investigation.

Registro Informatizado de Enfermedad Tromboembólica Investigators., [Objective] Overlap exists between the risk factors for coronary artery disease and venous thromboembolism (VTE). However, a paucity of data is available on the incidence of major acute cardiovascular events (MACE) and major adverse limb events (MALE) among patients presenting with VTE. Moreover, it is unknown whether the rate of cardiovascular outcomes differs among patients with unprovoked vs provoked VTE., [Methods] We analyzed the data from 2009 to 2017 in the Registro Informatizado de Enfermedad Tromboembólica registry, an ongoing, multicenter, international registry of consecutive patients with a diagnosis of objectively confirmed VTE. The query was restricted it to patients with data entry for the arterial outcomes. The baseline prevalence of coronary artery disease risk factors was compared between patients with provoked (ie, immobility, cancer, surgery, travel >6 hours, hormonal causes) and unprovoked VTE. After the initial VTE event, we followed up patients for the composite primary outcome of incident MACE (ie, stroke, myocardial infarction, unstable angina) and/or MALE (ie, major limb events). We used the χ2 test for baseline associations and a Cox proportional hazard for multivariate analysis. We used IBM SPSS, version 24 (IBM Corp, Armonk, NY) for statistical analysis. A P value of, [Results] We analyzed the data from 41,259 patients with VTE, of whom 22,633 (55.6%) had experienced a provoked VTE. During follow-up, the patients with provoked VTE were more likely to develop MACE or MALE than were patients with unprovoked VTE (hazard ratio [HR], 1.3; 95% confidence interval [CI], 1.1-1.5). The association of arterial events with recent immobility (HR, 1.4; 95% CI, 1.5-12.1) and cancer (HR, 1.7; 95% CI, 1.4-1.9) was strong. After adjusting for multiple conventional cardiovascular risk factors, provoked VTE, compared with unprovoked VTE, was significantly associated with an increased hazard for MACE (HR, 1.4; 95% CI, 1.1-1.7). Cancer remained a significant adjusted predictor for both MACE (HR, 1.7; 95% CI, 1.4-2.1) and MALE (HR, 2.1; 95% CI 1.01-4.6) in those with provoked VTE., [Conclusions] Among patients with VTE, provoked cases, specifically those with cancer-associated VTE, have an increased risk of major arterial events.

Essentials Ultrasound elastography uses tissue deformation to assess the relative quantification of its elasticity. Compression and duplex ultrasonography may be unable to correctly determine the thrombus age. Ultrasound elastography may be useful to distinguish between acute and chronic deep vein thrombosis. The exact determination of the thrombus age could have both therapeutic and prognostic implications. BACKGROUND: Background Ultrasound elastography (UE) imaging is a novel sonographic technique that is commonly employed for relative quantification of tissue elasticity. Its applicability to venous thromboembolic events has not yet been fully established; in particular, it is unclear whether this technique may be useful in determining the age of deep vein thrombosis (DVT). Thus, the aim of this study was to assess the role of UE in distinguishing acute from chronic DVT. Methods Consecutive patients with a first unprovoked acute and chronic (3 months old) DVT of the lower limbs were analyzed. Patients with recurrent DVT or with a suspected recurrence were excluded. The mean elasticity index (EI) values of acute and chronic popliteal and femoral vein thrombosis were compared. The accuracy of the EI in distinguishing acute from chronic DVT was also assessed by measuring the sensitivity, specificity, positive and negative predictive values, and likelihood ratios. Results One-hundred and forty-nine patients (mean age 63.9 years, standard deviation 13.6; 73 males) with acute and chronic DVT were included. The mean EI of acute femoral DVT was higher than that of chronic femoral DVT (5.09 versus 2.46), and the mean EI of acute popliteal DVT was higher than that of chronic popliteal DVT (4.96 versus 2.48). An EI value of > 4 resulted in a sensitivity of 98.9% (95% confidence interval [CI] 93.3-99.9), a specificity of 99.1% (95% CI 94.8-99.9), a positive predictive value of 91.1% (95% CI 77.9-97.1), a negative predictive value of 98.6% (95% CI 91.3-99.9), a positive likelihood ratio of 13.23 (95% CI 93-653) and a negative likelihood ratio of 0.001 (95% CI 0.008-0.05) for acute DVT. Conclusions UE appears to be a promising technique for distinguishing between acute and chronic DVT. Larger prospective studies are warranted to confirm our preliminary findings.

Abstract. As about 50 % of patients with unprovoked venous thromboembolism (VTE) will develop new episodes after discontinuing therapy, indefinite treatment is suggested in patients with low or moderate bleeding risk. Baseline and post-baseline factors can help clinicians to identify patients at high risk of recurrence, who require extended treatment. Residual vein obstruction and D-dimer assay have been shown to be suitable methods for assessing the risk of VTE recurrences after a first unprovoked VTE. In treatment for VTE the use of direct oral anticoagulants (DOAC) is growing instead of the standard adjusted dose of vitamin K antagonists. The DOAC safety profile has recently been strengthened with systematic reviews and meta-analyses. Idarucizumab is only approved for the reversal of dabigatran etexilate; intravenous antidotes for factor Xa inhibitors are under development. Their advent is of great interest. In the extended treatment of VTE sulodexide has been demonstrated to significantly decrease the risk of recurrences with an excellent safety profile. Aspirin is substantially less effective than oral anticoagulants in preventing recurrences but could play a role among patients who decided to stop anticoagulants. In conclusion, for the secondary prevention of VTE several options are available, without a recognised best choice regarding the treatment duration and the choice of drugs. An individual strategy taking into account risk of recurrence, bleeding risk, therapeutic options, and patient preferences is appropriate.

Introduction Whether women developing venous thromboembolism (VTE) while using hormonal therapy should be classified as having “unprovoked” or “provoked” VTE is controversial. Methods We used the RIETE (Registro Informatizado Enfermedad TromboEmbolica) database to compare the rate of symptomatic VTE recurrences after discontinuing anticoagulation in 3 subgroups of women aged ≤ 50 years without cancer, pregnancy or puerperium: (1) those with hormonal therapy and no additional risk factors (hormonal users only); (2) those with unprovoked VTE; and (3) those with additional risk factors, with or without hormonal therapy. Results As of March 2016, 1513 women had been followed-up for at least one month after discontinuing anticoagulation. Of these, 654 (43%) were hormonal users only, 390 (26%) had unprovoked VTE and 469 (31%) had transient risk factors with or without hormonal therapy. After discontinuing anticoagulation, the rate of VTE recurrences in women with hormonal use only (2.44 per 100 patient-years; 95% CI: 1.53–3.69) was significantly lower than in those with unprovoked VTE (6.03; 95% CI: 3.97–8.77) and similar to those with transient risk factors (2.58; 95% CI: 1.50–4.13). Interestingly, the rate of VTE recurrences presenting as pulmonary embolism in women with hormonal use only (0.55 per 100 patient-years; 95% CI: 0.18–1.29) was similar to those with transient risk factors (0.46; 95% CI: 0.09–1.33) and 4-fold lower than in women with unprovoked VTE (2.23; 95% CI: 1.07–4.10). Conclusions After discontinuing anticoagulation, the rate of VTE recurrences in hormonal users only was significantly lower than in women with unprovoked VTE and similar to the rate in women with additional risk factors.

inferior vena cava filters (IVCF) are widely used to prevent thromboembolic events in patients not suitable for anticoagulation (AC). Although new generations of filters are optional and therefore retrievable, most of them become permanent. Aim of our study was to evaluate real life IVCF management in a tertiary hospital including retrieval rates and reasons for permanent filtering.Electronic charts from patients receiving IVCF in a Swiss university hospital, during 1999-2017, were retrospectively identified. Patients were classified in two groups, according to filter retrieval (RG) or not (NRG). Type and reasons of filter placement were assessed. Retrieval, complications, and mortality rates were calculated. Reasons of non-retrieval were analyzed.920 patients received an IVCF during 1999-2017. Filters were retrieved in 372 patients (40.65%). Subjects in the NRG were significantly older, more chronically ill, and presented higher mortality rate at 12 months following filter insertion (29.60% vs. 4.30%; p 0.001). Reasons for non-retrieval included lack of follow-up (22.34%), persistent contraindications to AC (20.51%), technical issues (17.40%), and severe morbidity with short life expectancy (17.22%). Overall, complication rates after filter placement was 18.58%. Most reported complication was filter thrombosis (15.60%).In a real life setting, optional IVCF are still too often left in place indefinitely. Need for a systematic follow-up to ensure prompt filter retrieval is warranted. IVCF are not retrieved mostly in chronically and more severely ill patients, likely accounting for higher mortality in these subjects.

Distal deep venous thrombosis (DDVTs) is one of the “grey” areas of venous thromboembolism. There is a great heterogeneity in the diagnostic and therapeutic strategies between all the diagnostic centers. Studies doesn’t clarify the problem so it is not clear yet if there is any advantage in diagnosing and consequentially treating all the IDDVT. The 2012 ACCP guidelines suggested clinical observation for 2 weeks over initial anticoagulation (grade 2C) in patients with acute IDDVT without severe symptoms or risk factors for extension.

Chronic thromboembolic pulmonary hypertension (CTEPH) is an uncommon and late complication of pulmonary embolism resulting from misguided remodelling of residual pulmonary thromboembolic material and small-vessel arteriopathy. CTEPH is the only form of pulmonary hypertension (PH) potentially curable by pulmonary endarterectomy (PEA). Unfortunately, several patients have either an unacceptable risk-benefit ratio for undergoing the surgical intervention or develop persistent PH after PEA. Novel medical and endovascular therapies can be considered for them. The soluble guanylate cyclase stimulator riociguat is recommended for the treatment of patients with inoperable disease or with recurrent/persistent PH after PEA. Other drugs developed for the treatment of other forms of PH, as prostanoids, phosphodiesterase-5 inhibitors and endothelin receptor antagonists have been used in the treatment of CTEPH, with limited benefit. Balloon pulmonary angioplasty is a novel and promising technique and is progressively emerging from the pioneering phase. Highly specialized training level and complex protocols of postoperative care are mandatory to consolidate the technical success of the surgical and endovascular intervention.

Rivaroxaban is a direct and selective inhibitor of factor Xa. The randomized clinical trials EINSTEIN evaluated the efficacy and safety of rivaroxaban for the treatment of venous thromboembolism (VTE) proving that the drug was non-inferior to standard treatment. The aim of this survey was to describe how rivaroxaban was used in a group of "real-life" patients with VTE.Between June and October 2014, physicians collected aggregate data, through an online questionnaire, on consecutive patients affected by VTE and treated with rivaroxaban in the previous 6 months. Descriptive statistics were performed on the collected data.A total of 345 questionnaires were filled out. The mean age of patients was 62 years, with a low prevalence of concomitant diseases and/or pharmacological treatments. Deep vein thrombosis was diagnosed in 90% of patients and pulmonary embolism in 47%; only 48% was hospitalized. Rivaroxaban was prescribed at the recommended doses and/or regimen in no more than 60% of cases. In 96% of patients, the initial therapeutic plan did not require changes. Adherence to the therapeutic plan and overall patient satisfaction with therapy were high.Rivaroxaban was found easy to use and was highly appreciated by patients.

Introduction Whether there is an association between venous thromboembolism (VTE) and atherosclerosis is still controversial. Aims In a case–control study conducted on subjects older than 50, we assessed the prevalence of symptomatic or subclinical atherosclerosis in a group of unselected patients with unprovoked VTE, and compared it with that of patients with secondary VTE and of matched control individuals free from VTE disorders. Methods Cases and controls were enquired about the presence of previous symptomatic manifestations of atherosclerosis. Those with a negative history underwent the ultrasound assessment of carotid arteries following a standardized procedure. An intima-media thickness higher than 0.9 mm or the detection of at least one carotid plaque was regarded as a subclinical manifestation of atherosclerosis. After adjusting for age, gender and risk factors for atherosclerosis, we calculated the odds ratio (OR) for symptomatic or subclinical atherosclerosis in patients with unprovoked VTE as compared to those with secondary VTE and controls. Results We recruited 100 patients with unprovoked VTE, 100 with secondary VTE and 100 control individuals. In patients with unprovoked VTE, the adjusted OR for symptomatic or subclinical atherosclerosis was 5.1 (95% CI, 2.0 to 13.1) in comparison to patients with secondary VTE, and 14.5 (95% CI, 5.8 to 36.3) in comparison to controls. The prevalence of atherosclerosis was higher in patients with secondary VTE than in controls (OR, 3.1; 95% CI, 1.6 to 6.1). Conclusion The results of this study confirm the presence of a strong association between venous thrombosis and atherosclerosis.

The introduction of factor Xa inhibitors advocated the initiation of clinical trials that addressed the value of anticoagulation in patients with hemodynamically stable primary pulmonary embolism (PE). In the Matisse trial in patients with PE, fondaparinux administered at therapeutic doses followed by vitamin K antagonists (VKA) has shown a comparable efficacy and safety profile to that seen with intravenous adjusted-dose unfractionated heparin/VKA. A long-acting derivative of fondaparinux, idraparinux, failed to achieve similar results. On the other hand, the Cassiopea study revealed that once weekly injections of idrabiotaparinux, a slightly modified form of idraparinux, have similar efficacy and better safety profile compared to VKAs in the long-term treatment of patients with PE. However, the inconvenient parenteral administration of both fondaparinux and idrabiotaparinux limits their routine clinical use. The availability of antithrombotic compounds that can be administered orally in fixed dose, owing to their predictable pharmacokinetics and pharmacodynamics, and have a lower potential for drug and food interactions has opened new horizons for the treatment of patients with PE. The Einstein PE, Amplify and Hokusai studies, conducted with rivaroxaban, apixaban and edoxaban, respectively, showed that for the treatment of PE they possess a more favorable benefit-to-risk profile than the conventional antithrombotic drugs. In addition, rivaroxaban and apixaban make it possible to treat uncomplicated PE patients from the beginning, without the need for the parenteral administration of heparins or fondaparinux, and edoxaban allows the treatment of fragile patients with lower doses. All of them cover a wide spectrum of clinical presentations, including PE patients at intermediate risk.

Stratification of the individual bleeding risk prior to initiation of anticoagulation in patients with acute venous thromboembolism (VTE) has the potential to assist clinicians in making decisions about the proper intensity and duration of antithrombotic therapy. It is unclear which of the validated and internationally accepted scores recommended for the achievement of this important task has the best predictive value. We compared the predictive value of four validated scores (by Landefeld, Beyth, Kuijer and Ruiz-Gimenez, respectively) for the development of major bleeding complications occurring in the first 3 months in patients with acute VTE treated with conventional anticoagulation. Based on the population of RIETE Registry (international registry of patients with acute VTE), we identified those patients presenting all the required prognostic variables, and then calculated the ability of each score for predicting the bleeding risk. Of 40,265 eligible patients, we identified 8,717 meeting the recruitment criteria. Overall, 0.9 % of patients experienced at least one episode of major bleeding within 90 days of the index event. The proportion of patients classified as having a low risk varied between 1.2 and 3.7 %, that of patients having an intermediate risk between 76 and 93 %, and that of patients classified as having a high risk between 6.1 and 18 %. The area under the receiver operating characteristic ranged between 0.55 and 0.60, the positive predictive value between 1.5 and 3.2, and the likelihood ratio between 0.72 and 1.59. In conclusion, all four scores show a very low ability to predict the bleeding risk in patients with acute VTE undergoing conventional anticoagulation.

Objective:A relevant role is emerging for functional foods in cardiovascular prevention. Aim of this study was to assess the effect of a nutraceutical approach on lipid profile and inflammatory cytokines along with vascular remodeling in subjects in primary prevention for cardiovascular disease in a

The risk of recurrent thromboembolic disorders in the 10-year period following an episode of unprovoked venous thromboembolism (VTE) ranges between 30 and 50%, the rate being higher in patients with primary deep venous thrombosis (DVT) than in those with primary pulmonary embolism (PE). The clinical presentation with primary PE increases by more than three times the risk of a new PE episode over that with isolated DVT. Baseline parameters that increase this risk are the proximal location of DVT, obesity, old age and male sex, whereas the role of thrombophilia is controversial. An increasing role is played by post-baseline parameters such as the ultrasound assessment of residual vein thrombosis and the determination of D-dimer. While the latest international guidelines suggest indefinite anticoagulation for most patients with the first episode of unprovoked VTE, new scenarios are being offered by the identification of risk stratification models and by strategies that have the potential to help identify patients in whom anticoagulation can be safely discontinued, such as those that incorporate the assessment of D-dimer and residual vein thrombosis. New opportunities are being offered by low-dose aspirin, which has recently been reported to decrease by more than 30% the risk of recurrent events without increasing the bleeding risk; and especially by a few emerging anti-Xa and anti-IIa oral compounds, which are likely to induce fewer haemorrhagic complications than vitamin K antagonists while preserving at least the same effectiveness, do not require laboratory monitoring, and can be used immediately after the thrombotic episode.

The use of inferior vena cava filters to prevent pulmonary embolism is increasing mainly because of indications that appear to be unclearly codified and recommended. The evidence supporting this approach is often heterogeneous, and mainly based on observational studies and consensus opinions, while the insertion of an IVC filter exposes patients to the risk of complications and increases health care costs. Thus, several proposed indications for an IVC filter placement remain controversial. We attempt to review the proof on the efficacy and safety of IVC filters in several “special” clinical settings, and assess the robustness of the available evidence for any specific indication to place an IVC filter.

Several heart diseases are promoters of left-side cardiac thrombosis and could lead to arterial embolism. The same mechanism may be responsible for right-side cardiac thrombosis and therefore be a direct source of pulmonary embolism.Yasuoka et al. showed a higher incidence of perfusion defects in lung scan in patients with spontaneous echocontrast in the right atrium than in those without it (40% and 7% respectively; P=0.006). We recently assessed the prevalence of heart diseases in 11.236 consecutive patients older than 60 years discharged from Venetian hospitals with a diagnosis of pulmonary embolism. We observed a higher prevalence of all-cause heart diseases (odds ratio 1.26; 95% confidence interval, 1.13-1.40) in patients with a diagnosis of pulmonary embolism alone (secondary or unprovoked) compared with those discharged with a diagnosis of pulmonary embolism associated with deep vein thrombosis, generating the hypothesis that some specific heart diseases in older patients could themselves be a possible source of pulmonary emboli.Further prospective studies are required to confirm these findings, which have the potential to open new horizons for the interpretation and management of venous thromboembolic disease.

Background In up to 80% of patients with pulmonary embolism (PE) no peripheral symptomatic thrombosis can be identified. Whether the heart may represent a source of PE is unknown. Methods We conducted a cross-sectional survey of patients who were 60 years or older and were discharged from the hospitals of Veneto region, Italy between 2000 and 2006 with the diagnosis of PE. We compared the prevalence of several acute and chronic heart diseases in patients discharged with the diagnosis of PE alone with that of patients with co-occurring symptomatic peripheral deep venous thrombosis (PE/DVT). Results Out of 11,236 eligible patients, 9079 (81%) were discharged with the diagnosis of PE alone, and 2157 with that of PE/DVT. 3239 of the 9079 (35.7%) patients with isolated PE, and 666 of the 2157 (30.9%) with PE/DVT had at least one heart disease. The adjusted odds ratio (OR) for having at least one heart disease in patients with isolated PE as compared to those with PE/DVT was 1.26 (95% CI, 1.13–1.40). The heart diseases that significantly contributed to the study results were all-cause cardiomyopathies (adjusted OR, 2.31; 95% CI, 1.37–3.89), all-cause heart failure (1.82; 1.45–2.27), coronary heart disease (1.28; 1.08–1.52), and atrial fibrillation or flutter (1.28; 1.08–1.51). Conclusions There is an association between isolated PE and a number of heart diseases. The results of our survey generate the hypothesis that in older patients several heart diseases may directly account for the development of PE. Prospective studies are needed to confirm this hypothesis.

Background and Objectives A high incidence of atherosclerotic lesions and cardiovascular events has been reported in patients with spontaneous venous thromboembolism. Endothelial dysfunction is an early marker of atherosclerosis and has predictive value for ischemic events. We have evaluated endothelial function in patients with a history of spontaneous venous thromboembolism.Design and Methods Patients with a history of symptomatic, objectively confirmed, spontaneous venous thromboembolism were included in a case-control study. Exclusion criteria were any known risk factors for cardiovascular diseases, other conditions associated with endothelial dysfunction, estro-progestinic therapy or pregnancy. Controls were age-(±5 years) and sex-matched subjects with the same exclusion criteria but without previous venous thromboembolism. Endothelial function was evaluated by the non-invasive measurement of flow-mediated vasodilation of the brachial artery and of plasma markers of endothelium activation; platelet activation parameters were also measured.Results Twenty-eight cases (8 females; mean age 59±15 years) and 28 controls (8 females; mean age 58±15) were studied. Flow-mediated vasodilation was 3.5±0.6% in cases (95% CIs: 2.2 to 4.8) and 5.7±0.6% (4.2 to 6.8) in controls (p=0.015). Brachial artery blood flow and hyperemic blood flow did not differ between the two groups. Plasma von Willebrand factor and soluble P-selectin levels were significantly higher in patients with venous thromboembolism, while plasma soluble CD40 ligand and urinary 11-dehydro-TxB2 levels were similar in cases and controls.Interpretation and Conclusions Patients with spontaneous venous thromboembolism have endothelial dysfunction, unlike age- and sex- matched controls. This finding suggests that spontaneous venous thromboembolism may be a condition associated with an enhanced risk of atherosclerosis.

While it has long been recognized that patients with acute unprovoked deep vein thrombosis (DVT) or pulmonary embolism (PE) have a higher risk of recurrent venous thromboembolism (VTE) than that of patients with secondary thrombosis, whether other clinical parameters can help predict the development of recurrent events is controversial. The aim of this investigation was to assess the rate of recurrent VTE after withdrawal of vitamin K antagonists, and to identify clinical parameters associated with a higher likelihood of recurrence.We followed, up to a maximum of 10 years, 1626 consecutive patients who had discontinued anticoagulation after a first episode of clinically symptomatic proximal DVT and/or PE. All patients with clinically suspected recurrent VTE underwent objective tests to confirm or rule out the clinical suspicion.After a median follow-up of 50 months, 373 patients (22.9%) had had recurrent episodes of VTE. The cumulative incidence of recurrent VTE was 11.0% (95% CI, 9.5-12.5) after 1 year, 19.6% (17.5-21.7) after 3 years, 29.1% (26.3-31.9) after 5 years, and 39.9% (35.4-44.4) after 10 years. The adjusted hazard ratio for recurrent VTE was 2.30 (95% CI, 1.82-2.90) in patients whose first VTE was unprovoked, 2.02 (1.52-2.69) in those with thrombophilia, 1.44 (1.03-2.03) in those presenting with primary DVT, 1.39 (1.08-1.80) for patients who received a shorter (up to 6 months) duration of anticoagulation, and 1.14 (1.06-1.12) for every 10-year increase of age. When the analysis was confined to patients with unprovoked VTE the results did not change.Besides unprovoked presentation, other factors independently associated with a statistically significant increased risk of recurrent VTE are thrombophilia, clinical presentation with primary DVT, shorter duration of anticoagulation, and increasing age.

Summary. Objective: The results of recent studies have suggested that patients with idiopathic venous thromboembolism (VTE) might be at increased risk of asymptomatic atherosclerosis and cardiovascular events. The metabolic syndrome is a cluster of risk factors for atherosclerosis. Its impact on VTE is unknown. Methods: In a case–control study, consecutive patients with objectively confirmed deep vein thrombosis (DVT) and control subjects with objectively excluded DVT underwent clinical assessment for the presence of the metabolic syndrome according to the National Cholesterol Education Program criteria. The presence of known risk factors for DVT was documented. Patients with DVT secondary to cancer were excluded. The prevalence of the metabolic syndrome was compared between patients with idiopathic DVT and controls. Results: We enrolled 93 patients with a first episode of idiopathic DVT and 107 controls. The mean age was 65.1 and 63.7 years, respectively. The metabolic syndrome was diagnosed in 50.5% of patients with idiopathic DVT and in 34.6% of controls [odds ratio (OR) 1.93; 95% confidence interval (CI) 1.05, 3.56]. After adjustment for age, sex, body mass index, and smoke, the metabolic syndrome remained independently associated with idiopathic DVT (OR 1.94; 95% CI 1.04, 3.63). In patients with secondary DVT, the prevalence of the metabolic syndrome was 27%. Conclusions: The metabolic syndrome may play a role in the pathogenesis of idiopathic DVT and may act as link between venous thrombosis and atherosclerosis.

Post-thrombotic syndrome (PTS) and chronic thromboembolic pulmonary hypertension (CTEPH) are late complications of venous thromboembolism. The purpose of this review is to present and discuss recently published studies that have improved our knowledge of PTS and CTEPH. The current understanding of the pathophysiology of PTS and CTEPH is discussed as well as the importance of chronic residual venous thrombosis, some polymorphisms of plasminogen activator inhibitor-1, and the current concept of misguided thrombus resolution. The surprising finding that elastic compression stockings may not be effective in preventing PTS and the novel medical treatment in CTEPH are discussed in detail. Novel direct oral anticoagulants show potential for prevention of PTS. No firm conclusions can be drawn on the efficacy of elastic stockings. Novel treatments of CTEPH for inoperable patients and those with persistent pulmonary hypertension after surgery have become available and further research on wider indication for their use is urgently needed.

SummaryOnce anticoagulation is stopped, the risk of recurrent venous thromboembolism (VTE) over years after a first episode is consistently around 30%. This risk is higher in patients with unprovoked than in those with (transient) provoked VTE, and among the latter in patients with medical than in those with surgical risk factors. Baseline parameters that have been found to be related to the risk of recurrent VTE are the proximal location of deep-vein thrombosis, obesity, old age, male sex and non-0 blood group, whereas the role of inherited thrombophilia is controversial. The persistence of residual vein thrombosis at ultrasound assessment has consistently been shown to increase the risk, as do persistently high values of D-dimer and the early development of the post-thrombotic syndrome. Although the latest international guidelines suggest indefinite anticoagulation for most patients with the first episode of unprovoked VTE, strategies that incorporate the assessment of residual vein thrombosis and D-dimer have the potential to identify subjects in whom anticoagulation can be safely discontinued. Moreover, new opportunities are offered by a few emerging anti-Xa and anti-IIa oral compounds, which are likely to induce fewer haemorrhagic complications than vitamin K antagonists while preserving the same effectiveness; and by low-dose aspirin, which has the potential to prevent the occurrence of both venous and arterial thrombotic events.

The diagnosis of pulmonary embolism (PE) is frequently considered in patients presenting to the emergency department or when hospitalized. Although early treatment is highly effective, PE is underdiagnosed and, therefore, the disease remains a major health problem. Since symptoms and signs are non specific and the consequences of anticoagulant treatment are considerable, objective tests to either establish or refute the diagnosis have become a standard of care. Diagnostic strategy should be based on clinical evaluation of the probability of PE. The accuracy of diagnostic tests for PE are high when the results are concordant with the clinical assessment. Additional testing is necessary when the test results are inconsistent with clinical probability. The present review article represents the consensus-based recommendations of the Interdisciplinary Association for Research in Lung Disease (AIMAR) multidisciplinary Task Force for diagnosis and treatment of PE. The aim of this review is to provide clinicians a practical diagnostic and therapeutic management approach using evidence from the literature.

SummaryRecently, a diagnostic strategy using a clinical decision rule, D-dimer testing and spiral computed tomography (CT) was found to be effective in the evaluation of patients with clinically suspected pulmonary embolism (PE). However, the rate of venous thromboembolic complications in the three-month follow-up of patients with negative CT was still substantial and included fatal events. It was the objective to evaluate the safety of withholding anticoagulants after a normal 64-detector row CT (64-DCT) scan from a cohort of patients with suspected PE. A total of 545 consecutive patients with clinically suspected first episode of PE and either likely pre-test probability of PE (using the simplified Wells score) or unlikely pre-test probability in combination with a positive D-dimer underwent a 64-DCT. 64-DCT scanning was inconclusive in nine patients (1.6%), confirmed the presence of PE in 169 (31%), and ruled out the diagnosis in the remaining 367. During the three-month follow-up of the 367 patients one developed symptomatic distal deep-vein thrombosis (0.27%; 95%CI, 0.0 to 1.51%) and none developed PE (0 %; 95%CI, 0 to 1.0%). We conclude that 64-DCT scanning has the potential to safely exclude the presence of PE virtually in all patients presenting with clinical suspicion of this clinical disorder.

BACKGROUND The optimal duration of oral anticoagulant therapy in patients with deep venous thrombosis (DVT) of the lower extremities remains uncertain. OBJECTIVE To assess whether tailoring the duration of anticoagulation on the basis of the persistence of residual thrombi on ultrasonography reduces the rate of recurrent venous thromboembolism (VTE) compared with the administration of conventional fixed-duration treatment in adults with proximal DVT. DESIGN Parallel, randomized trial from 1999 to 2006. Trained physicians who assessed outcomes were blinded to patient assignment status, but patients and providers were not. SETTING 9 university or hospital centers in Italy. PATIENTS 538 consecutive outpatients with a first episode of acute proximal DVT at completion of an uneventful 3-month period of anticoagulation. INTERVENTION Patients were randomly assigned (stratified by center and secondary vs. unprovoked DVT by using a computer-generated list that was accessible only to a trial nurse) to fixed-duration anticoagulation (no further anticoagulation for secondary thrombosis and an extra 3 months for unprovoked thrombosis) or flexible-duration, ultrasonography-guided anticoagulation (no further anticoagulation in patients with recanalized veins and continued anticoagulation in all other patients for up to 9 months for secondary DVT and up to 21 months for unprovoked thrombosis). For the primary outcome assessment, 530 patients completed the trial. MEASUREMENTS The rate of confirmed recurrent VTE during 33 months of follow-up. RESULTS Overall, 46 (17.2%) of 268 patients allocated to fixed-duration anticoagulation and 32 (11.9%) of 270 patients allocated to flexible-duration anticoagulation developed recurrent VTE (adjusted hazard ratio [HR], 0.64 [95% CI, 0.39 to 0.99]). For patients with unprovoked DVT, the adjusted HR was 0.61 (CI, 0.36 to 1.02) and 0.81 (CI, 0.32 to 2.06) for those with secondary DVT. Major bleeding occurred in 2 (0.7%) patients in the fixed-duration group and 4 (1.5%) patients in the flexible-duration group (P = 0.67). LIMITATIONS The trial lacked a double-blind design. The sample size was not powered to detect differences in bleeding between groups and to detect effectiveness of the intervention in the subgroups of patients with unprovoked and secondary DVT. Patients with previous thromboembolism, permanent risk factors for thrombosis, and thrombophilic abnormalities other than factor V Leiden and prothrombin mutation were excluded. CONCLUSION Tailoring the duration of anticoagulation on the basis of ultrasonography findings reduces the rate of recurrent VTE in adults with proximal DVT. PRIMARY FUNDING SOURCE None.

Following deep vein thrombosis (DVT), one of every two patients will develop postthrombotic syndrome (PTS), which causes remarkable consequences on the socioeconomic level. Residual thrombosis is an important predictor of PTS, and severe early symptoms, old age, obesity, improper anticoagulation, recurrent thrombosis and varicose veins are major risk factors. Diagnosis of PTS is mainly based on the clinical findings for patients with a history of DVT, while in those without it, instrumental diagnosis might help in detecting a previous DVT. Prompt administration of adequate compression elastic stockings (ECS) in patients with symptomatic DVT reduces the frequency of PTS by half. Usually, the management of an established PTS is demanding, and often discouraging. However, when carefully supervised and instructed to wear proper ECS, more than 50% of patients either remain quiescent or improve during long-term follow-up.

In up to 80% of patients with pulmonary embolism (PE) no peripheral symptomatic thrombosis can be identified. Whether the heart may represent a source of PE is unknown.We conducted a cross-sectional survey of patients who were 60 years or older and were discharged from the hospitals of Veneto region, Italy between 2000 and 2006 with the diagnosis of PE. We compared the prevalence of several acute and chronic heart diseases in patients discharged with the diagnosis of PE alone with that of patients with co-occurring symptomatic peripheral deep venous thrombosis (PE/DVT).Out of 11,236 eligible patients, 9079 (81%) were discharged with the diagnosis of PE alone, and 2157 with that of PE/DVT. 3239 of the 9079 (35.7%) patients with isolated PE, and 666 of the 2157 (30.9%) with PE/DVT had at least one heart disease. The adjusted odds ratio (OR) for having at least one heart disease in patients with isolated PE as compared to those with PE/DVT was 1.26 (95% CI, 1.13-1.40). The heart diseases that significantly contributed to the study results were all-cause cardiomyopathies (adjusted OR, 2.31; 95% CI, 1.37-3.89), all-cause heart failure (1.82; 1.45-2.27), coronary heart disease (1.28; 1.08-1.52), and atrial fibrillation or flutter (1.28; 1.08-1.51).There is an association between isolated PE and a number of heart diseases. The results of our survey generate the hypothesis that in older patients several heart diseases may directly account for the development of PE. Prospective studies are needed to confirm this hypothesis.

Pulmonary embolism (PE) is a common condition carrying a significant degree of mortality if not diagnosed early. The diagnosis of PE is challenging, because of the non-specific nature of its clinical features. For many years the diagnostic strategies for PE have mainly involved ventilation/perfusion lung scan as the chief diagnostic procedure, often associated with a few clinical models of pre-test probability and the D-dimer test. These modalities of diagnosing PE, though quite satisfactory in various clinical settings, show several limitations, the most important one being the high rate of non-diagnostic procedures. The introduction of computed tomography (CT) has changed the diagnostic strategies and has become the main diagnostic procedure for diagnosing PE. CT is undergoing a rapid technological upgrade, which will open in the near future new frontiers in the diagnosis of PE. Nonetheless, CT carries a number of limitations, which should be carefully identified. This article reviews the evidences on both the traditional and newer diagnostic strategies for PE, outlines their strengths and weaknesses and describes future applications of CT for diagnosing PE.