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The impact of residual pulmonary obstruction on the outcome of patients with pulmonary embolism is uncertain.We recruited 647 consecutive symptomatic patients with a first episode of pulmonary embolism, with or without concomitant deep venous thrombosis. They received conventional anticoagulation, were assessed for residual pulmonary obstruction through perfusion lung scanning after 6 months and then were followed up for up to 3 years. Recurrent venous thromboembolism and chronic thromboembolic pulmonary hypertension were assessed according to widely accepted criteria.Residual pulmonary obstruction was detected in 324 patients (50.1%, 95% CI 46.2–54.0%). Patients with residual pulmonary obstruction were more likely to be older and to have an unprovoked episode. After a 3-year follow-up, recurrent venous thromboembolism and/or chronic thromboembolic pulmonary hypertension developed in 34 out of the 324 patients (10.5%) with residual pulmonary obstruction and in 15 out of the 323 patients (4.6%) without residual pulmonary obstruction, leading to an adjusted hazard ratio of 2.26 (95% CI 1.23–4.16).Residual pulmonary obstruction, as detected with perfusion lung scanning at 6 months after a first episode of pulmonary embolism, is an independent predictor of recurrent venous thromboembolism and/or chronic thromboembolic pulmonary hypertension.

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.

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.

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 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.

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.

The separate nature of venous and arterial thrombotic disorders has recently been challenged. Patients with venous thromboembolism (VTE) have an increased risk of subsequent symptomatic arterial cardiovascular events, the risk being higher in those with unexplained episodes. Among the implications of this association, there is the potential for old and new antithrombotic drugs to impact on the development of both venous and arterial cardiovascular events. According to the results of recent studies, aspirin in low doses, when administered for the long-term management of patients with unprovoked VTE, reduces by approximately 35% the risk of recurrent VTE while offering a considerable protection against the development of arterial cardiovascular events. By contrast, there is no room to expect a reduction in the risk of subsequent arterial cardiovascular events in patients treated with vitamin K antagonists (VKA) in comparison to patients in whom VKAs are discontinued. According to the results from recent randomized clinical trials, the likelihood of arterial cardiovascular events in patients on the novel direct factor Xa inhibitors is unlikely to differ from that of patients receiving conventional anticoagulation. As dabigatran has been associated with a slight increase in the risk of myocardial infarction over warfarin, its use should be discouraged in patients with coronary heart disease. The long-term use of low-dose apixaban beyond the first months in patients with unprovoked VTE may decrease the long-term risk of arterial, as well as venous, thrombotic events.

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.

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.

Residual vein thrombosis and trans-popliteal reflux in patients with and without the post-thrombotic syndrome

An increasing body of evidence suggests the likelihood of a link between venous and arterial thrombosis. The two vascular complications share several risk factors, such as age, obesity, smoking, diabetes mellitus, blood hypertension, hypertriglyceridemia, and metabolic syndrome. Moreover, there are many examples of conditions accounting for both venous and arterial thrombosis, such as the antiphospholipid antibody syndrome, hyperhomocysteinemia, malignancies, infections, and the use of hormonal treatment. Finally, several recent studies have consistently shown that patients with venous thromboembolism are at a higher risk of arterial thrombotic complications than matched control individuals. We, therefore, speculate the two vascular complications are simultaneously triggered by biological stimuli responsible for activating coagulation and inflammatory pathways in both the arterial and the venous system. Future studies are needed to clarify the nature of this association, to assess its extent, and to evaluate its implications for clinical practice.

Background— Heart diseases increase the risk of arterial embolism; whether they increase the risk of pulmonary embolism without peripheral venous thrombosis is less certain. Methods and Results— We conducted a nationwide, population-based case-control study in Denmark using patients diagnosed with pulmonary embolism and/or deep venous thrombosis between 1980 and 2007. We computed odds ratios to estimate relative risks associating preceding heart disease with pulmonary embolism, pulmonary embolism and deep venous thrombosis, or deep venous thrombosis alone. In this study, 45 282 patients had pulmonary embolism alone, 4680 had pulmonary embolism and deep venous thrombosis, and 59 790 had deep venous thrombosis alone; 541 561 were population controls. Myocardial infarction and heart failure in the preceding 3 months conferred high risks of apparently isolated pulmonary embolism (odds ratio, 43.5 [95% confidence interval (CI), 39.6–47.8] and 32.4 [95% CI, 29.8–35.2], respectively), whereas the risks of combined pulmonary embolism and deep venous thrombosis (19.7 [95% CI, 16.0–24.2] and 22.1 [95% CI, 18.7–26.0], respectively) and deep venous thrombosis alone (9.6 [95% CI, 8.6–10.7] and 12.7 [95% CI, 11.6–13.9], respectively) were lower. Left-sided valvular disease was associated with an odds ratio of 13.5 (95% CI, 11.3–16.1), whereas the odds ratio was 74.6 (95% CI, 28.4–195.8) for right-sided valvular disease. Restricting the analysis to cases diagnosed after 2000 led to lower risk estimates but the same overall pattern. Conclusion— Heart diseases increase the near-term risk for pulmonary embolism not associated with diagnosed peripheral vein thrombosis.

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.

About 10% of all episodes of venous thrombosis are due to upper extremity deep vein thrombosis (UEDVT). Associated risk factors are indwelling central venous catheters, cancer, and coagulation defects; 20% of the episodes are unexplained. The onset of UEDVT is usually heralded by complaints such as arm swelling and pain, but may also be completely asymptomatic, especially in carriers of central venous lines. Objective confirmation is mandatory prior to instituting anticoagulation because the clinical diagnosis is unreliable; ultrasound-based methods represent the preferred diagnostic approach. Prophylaxis with low-dose heparin or low-dose warfarin may be used, especially in carriers of central venous catheters, although its efficacy is still uncertain. Unfractionated or low molecular weight heparins followed by oral anticoagulants should be regarded as the treatment of choice, whereas thrombolysis and surgery may be indicated in selected cases. Up to one third of the patients develop pulmonary embolism that may be fatal; postthrombotic syndrome and recurrent thromboembolism are also frequent complications. UEDVT should no longer be regarded as a rare and benign disease, as reported previously.

Despite considerable progress in the diagnosis and treatment of deep vein thrombosis (DVT) of the lower extremities, one of every three patients will develop postthrombotic sequelae within 2 years; these sequelae are severe in approximately 20% of cases and produce considerable socioeconomic consequences. Among factors potentially related to the development of the postthrombotic syndrome (PTS) are older age, obesity, insufficient oral anticoagulant therapy, and recurrent ipsilateral thrombosis. Whether the extent and location of the initial thrombosis are associated with the development of PTS is controversial. Based on recent findings, the lack of vein recanalization within the first 6 months appears to be an important predictor of PTS, whereas the development of transpopliteal venous reflux is not. The diagnosis of PTS can be made on clinical grounds for patients with a history of DVT. The combination of a standardized clinical evaluation with the results of compression ultrasonography and Doppler ultrasound helps diagnose or exclude a previous proximal vein thrombosis. According to the results of recent clinical studies, the prompt administration of adequate compression elastic stockings in patients with symptomatic DVT has the potential to reduce the frequency of late PTS development by half. The management of this condition is demanding and often frustrating. However, when carefully supervised and instructed to wear proper elastic stockings, more than 50% of patients will either remain stable or improve during long-term follow-up. Clinical presentation helps predict the prognosis; the outcome of patients who refer with initially severe manifestations is more favorable than that of patients whose symptoms deteriorate progressively over time.

Study objective To assess the incidence of chronic thromboembolic pulmonary hypertension (CTPH) after the first episode of objectively confirmed pulmonary embolism (PE). Design Prospective cohort study in 12 Italian medical centers. Patients Consecutive patients treated with oral anticoagulants for the first episode of PE, either idiopathic or associated with temporary risk factors, were followed up for at least 3 years. Patients were excluded from the study if they had a known persistent risk factor for venous thromboembolism (VTE). Interventions At the follow-up visits, patients were evaluated for persistent dyspnea, either at rest or on exertion. All patients who were referred with dyspnea were assessed by transthoracic echocardiography, with evaluation of the systolic and mean pulmonary artery pressures. Patients with evidence of pulmonary hypertension on echocardiography underwent perfusion lung scans and pulmonary angiography to confirm the diagnosis of CTPH. Results Overall, 259 patients were included in the study. PE was idiopathic in 135 patients, while it was associated with at least a temporary risk factor for VTE in 124 patients. After an average follow-up period of 46 months, 37 patients were found to have persistent dyspnea that was unexplained in 5 patients. Among these patients, a diagnosis of CTPH was confirmed in two patients with idiopathic PE (0.8% of the overall study population [95% confidence interval (CI), 0.0 to 1.9]; 1.5% of patients with idiopathic PE [95% CI, 0.0 to 3.6]). The diagnosis was made 14 and 22 months, respectively, after the acute PE. Conclusions The incidence of CTPH observed in this study was about 1%. CTPH was observed in two patients with idiopathic PE.

1928–30. Summary. Background: Recently, we reported an association between asymptomatic carotid atherosclerosis and venous thromboembolism (VTE) of unknown origin. We hypothesized that patients with VTE of unknown origin would be at a higher risk of developing symptomatic atherosclerosis than patients with VTE induced by known risk factors. Methods: To examine this hypothesis, we studied 1919 consecutive patients followed prospectively after their first VTE episode. The primary outcome was non-fatal and fatal symptomatic atherosclerotic disease in patients with VTE of unknown origin as compared to those with secondary VTE. An independent committee assessed all study outcomes, and adjusted hazard ratios (HR) were calculated using the Cox’s proportional hazards model. Results: After a median follow-up of 48 and 51 months, respectively, at least one symptomatic atherosclerotic complication was detected in 160 of the 1063 patients (15.1%) with VTE of unknown origin, and in 73 of the 856 (8.5%) with secondary VTE. After adjusting for age and other risk factors of atherosclerosis, the HR for symptomatic atherosclerotic complications in patients with VTE of unknown origin compared to those with secondary VTE was 1.6 (95% confidence intervals; CI: 1.2–2.0). When the analysis was restricted to patients without previous symptomatic atherosclerosis, the HR became 1.7 (95% CI: 1.1–2.4). Conclusions: Patients with VTE of unknown origin have a 60% higher risk of developing symptomatic atherosclerotic disease than do patients with secondary venous thrombosis.

Although spiral computed tomography (CT) is being used increasingly as the first-line imaging procedure in the diagnostic workup of patients with clinically suspected pulmonary embolism (PE), the diagnostic value of negative findings, at least when using the four-detector row scanners, is still controversial. A total of 702 consecutive patients with clinical symptoms suggestive of PE underwent four-slice CT. Patients with negative findings received the determination of D-dimer. Those with positive D-dimer underwent further diagnostic workup to confirm or rule out the diagnosis of PE. Those with negative D-dimer were followed-up to 6 months to detect the development of symptomatic venous thromboembolism (VTE). The CT test was interpreted as negative in 536 patients (76.3%). These patients had the D-dimer determination, which was positive in 279 and negative in the remaining 257 patients. Of the former, PE subsequently was documented in 55 patients (19.7%). Of the latter, symptomatic VTE in the follow-up period developed in three patients (1.17%; 95% confidence interval, 0.24 to 3.38%). In conclusion, when using the four-detector row, the negative predictive value of CT findings in patients with clinically suspected PE and positive D-dimer is low. In contrast, it is safe to withhold anticoagulation from patients with negative findings and negative D-dimer.

In recent years, new opportunities have emerged that have the potential to change rapidly the therapeutic scenario of patients with acute venous thromboembolism (VTE). Selected patients with deep vein thrombosis (DVT) can be treated effectively and safely at home with fixed doses of low molecular weight heparins. The prompt administration of compression elastic stockings in addition to anticoagulant drugs in patients with acute DVT has the potential to halve the rate of late postthrombotic sequelae. The long-term use of low molecular weight heparins is likely to be more effective than oral anticoagulants for the secondary prevention of VTE in patients with advanced malignancy. Patients with pulmonary embolism and right ventricular dysfunction might benefit from the early administration of thrombolytic drugs in combination with heparin to a greater extent than from heparin alone. Despite an impressive amount of clinical information on the proper duration of oral anticoagulants in patients with unprovoked VTE, the optimal long-term treatment of these patients remains undefined. Finally, new categories of drugs are emerging that have the potential to replace conventional anticoagulants in the near future. They include compounds that inhibit factor Xa or thrombin.

The aim of this prospective study was to assess the effectiveness and the long-term patency effect of excimer laser angioplasty in peripheral arterial obstructive disease. Seventy-eight patients referred for excimer laser angioplasty of lower limbs have been followed up for up to 24 months. Ankle/brachial systolic pressure index, color Doppler mapping, and arterial digital subtraction angiography were performed. Immediate proce dural success was achieved in a high percentage of patients (97%). Balloon angioplasty was also used in 85% of patients. Early reocclusions occurred in 8% of patients. The cumulative patency rate was 47% at the 12-month interval and 40% at the 24-month interval. Poor runoff and the length of the lesions negatively influenced the outcome. Excimer laser angioplasty is an effective procedure, indicated in selected patients showing < 10 cm occlusions and good runoff.

Objective To evaluate whether pulmonary embolism (PE), as detected by perfusion lung scan, could be predicted by the ultrasonic (US) characteristics of the thrombi in patients with deep venous thrombosis (DVT) of the lower limbs. Patients Ninety-three consecutive patients with DVT and no symptoms of lung involvement (52 men, 41 women; mean age, 67±17 years). Measurements and Results The degree of thrombotic involvement of the lower limbs was assessed using a US score system ranging from 1 (indicating a subsegmental, nonocclusive thrombus) to 16 (massive, occlusive). According to the echographic and color-Doppler features, the thrombi were classified in terms of echoreflectivity, adhesiveness to the vein wall, and organization. The diagnosis of PE (PIOPED criteria) was highly probable in 46% of the patients, intermediate in 15%, low in 8%, and very low/normal in 31%. No correlations were found between the lung scan findings on one side and the venous scoring system or the US features of the thrombi on the other side. Conclusions While confirming that the prevalence of PE in patients with DVT is elevated, we failed to define a subgroup of patients at higher risk. Our data imply that lung scan should be used extensively for the detection of silent PE and that anticoagulation should not be graded on US findings.

Ninety-four consecutive patients (60 men and 34 women; mean age 68.5 ± 11.5 years) with acute myocardial infarction (MI) were investigated ret rospectively, in order to evaluate the prevalence, clinical features, and short- term course of the atypical forms (symptoms other than chest pain). An atypical MI was found in 30 patients, with a prevalence of 32% (95% confidence limits 27-36%). It was most prevalent in women above sixty-five years old (P < 0.05). Abdominal pain, paroxysmal dyspnea, and pulmonary edema were the most frequent symptoms (33%, 17%, 13%, respectively). No differences were ob served between typical and atypical MI in regard to risk factors (hypercholes terolemia, arterial hypertension, diabetes mellitus, cigarette smoking) and history of MI, cerebrovascular disease, peripheral vascular disease, or chronic lung disease. Significantly fewer patients with atypical MI had a history of an gina pectoris (P < 0.05). No differences were observed in regard to previous medication, except for antiarrhythmic drugs, more often used by atypical pa tients (P < 0.05). Location and severity of MI (as judged by ECG and peak levels of creatine kinase in the serum) were similar in both subgroups, as were the complications (34% typical and 50% atypical) and death rate (12.5% and 16.7%, respectively). In conclusion, atypical MI is not less severe than typical. This emphasizes the need for a high suspicion index in many different clinical settings, but particu larly (although not exclusively) in elderly females, in the presence of abdominal pain or otherwise unexplained paroxysmal dyspnea.

The purpose of the present study was to evaluate the role of color flow du plex imaging (CFDI) in the follow-up of patients who have undergone excimer- laser-assisted angioplasty of peripheral arteries. Sixty-one patients (40 men and 21 women) were studied (mean age ± SD sixty-three ± nine years). All patients were affected by peripheral vascular dis ease and, for this reason, underwent percutaneous excimer-laser-assisted angio plasty. Digital angiography and CFDI were performed before the laser procedure. CFDI was repeated at months 1, 3, 6, 9, and 12 after the laser procedure, whereas angiography was repeated after twelve months. Common, superficial, and profunda femoral arteries and popliteal arteries were visualized in looking for the presence of lesions and occlusions, and spectral analysis of Doppler signals was recorded. After the initial success, claudication was reported again by 9 patients, 7 of whom showed total occlusions. All reocclusions were discovered by CFDI and confirmed by angiography; 3 of these 7 patients underwent a second laser pro cedure. The remaining 2 symptomatic patients showed patent vessels and did not undergo angiography. Another 9 patients redeveloped an occlusion, unsus pected from clinical history and symptoms. All the reocclusions, confirmed by angiography, were diagnosed by CFDI. The data show that CFDI provides an accurate noninvasive technique for following up patients after excimer laser angioplasty, allowing for asymptomatic reocclusions to be recognized and treated if necessary, and permitting symptoms not due to reocclusions to be properly identified, thus avoiding unnecessary angiography.