T. van der Hulle

Effectiveness and safety of novel oral anticoagulants as compared with vitamin K antagonists in the treatment of acute symptomatic venous thromboembolism: a systematic review and meta‐analysis

New direct oral anticoagulants (NOACs) constitute a novel treatment option for acute venous thromboembolism (VTE), with practical advantages. Individual studies have demonstrated comparable efficacy to that of vitamin K antagonists (VKAs) and have suggested a more favorable safety profile . We performed a meta‐analysis to determine the efficacy and safety of NOACs as compared with those of VKAs in patients with acute VTE.

The post-PE syndrome: a new concept for chronic complications of pulmonary embolism

Long-term follow-up studies have consistently demonstrated that after an episode of acute pulmonary embolism (PE), half of patients report functional limitations and/or decreased quality of life up to many years after the acute event. Incomplete thrombus resolution occurs in one-fourth to one-third of patients. Further, pulmonary artery pressure and right ventricular function remain abnormal despite adequate anticoagulant treatment in 10-30% of patients, and 0.5-4% is diagnosed with chronic thromboembolic pulmonary hypertension (CTEPH) which represents the most severe long term complication of acute PE. From these numbers, it seems that CTEPH itself is the extreme manifestation of a much more common phenomenon of permanent changes in pulmonary artery flow, pulmonary gas exchange and/or cardiac function caused by the acute PE and associated with dyspnea and decreased exercise capacity, which in analogy to post-thrombotic syndrome after deep vein thrombosis could be referred to as the post-pulmonary embolism syndrome. The acknowledgement of this syndrome would both be relevant for daily clinical practice and also provide a concept that aids in further understanding of the pathophysiology of CTEPH. In this clinically oriented review, we discuss the established associations and hypotheses between the process of thrombus resolution or persistence, lasting hemodynamic changes following acute PE as well as the consequences of a PE diagnosis on long-term physical performance and quality of life.

Computed tomography-assessed right ventricular dysfunction and risk stratification of patients with acute non-massive pulmonary embolism: systematic review and meta-analysis.

The ability of computed tomography (CT)‐assessed right ventricular dysfunction (RVD) to identify normotensive patients with acute pulmonary embolism (PE) at high risk of mortality or adverse outcome lacks clarity.

Long-term clinical course of acute pulmonary embolism.

The long-term clinical course of acute pulmonary embolism (PE) is complicated by high rates of serious adverse events, both before and after cessation of anticoagulant therapy. These adverse events include recurrent venous thromboembolism, chronic thromboembolic pulmonary hypertension, arterial thrombotic events and increased risk of death, all compared to patients without thromboembolic disease. Several pharmacological options are available that may beneficially influence patients prognosis. Nonetheless, because of insufficient knowledge of the benefit-to-harm ratio of these pharmacological agents, unambiguous recommendations are scarcely available. This review will cover the epidemiological aspects of the various possible complications in the long-term clinical course of acute PE as well as the latest evidence on preventive strategies. In addition, the unresolved issues regarding frequency, duration and focus of medical follow-up after acute PE are discussed.

Embolic burden of incidental pulmonary embolism diagnosed on routinely performed contrast-enhanced computed tomography imaging in cancer patients.

Since the quality of computed tomography (CT) imaging techniques has improved, pulmonary embolism (PE) has increasingly been detected incidentally on routine CT examination. In particular, in patients with malignancy, who are known to be at elevated risk of developing venous thromboembolic events, and who frequently undergo CT scanning for reasons such as diagnosing, staging, and treatment evaluation, incidental PE has become a relatively common finding [1]. There is limited information on the embolic burden in patients in whom PE goes clinically unnoticed. It may be theorized that, in patients without symptoms suggestive of PE, the emboli may more frequently be localized distally, leading to a smaller obstruction index. The first aim of the present study was to assess the embolic burden of patients with incidental PE and compare it with that of patients with symptomatic PE. The second aim was to assess the impact of the embolic burden on the outcome of the patients. Consecutive adult patients with active malignancy who received a diagnosis of incidental PE between January 2003 and July 2012 in our hospital were included. The characteristics of this cohort have, in part, been described previously [2]. Incidental PE was defined as a diagnosis of PE detected on CT scans ordered for reasons other than suspected PE [3]. Institutional review board approval was waived for this observational and retrospective study. Imaging was performed with multidetector CT scanners (four-slice, 16-slice, 64-slice and 320-slice CT scanners; Toshiba, Otawara, Japan). Images were reconstructed with a slice thickness of 1.0 mm. All CT images were reviewed on a PACS workstation by an experienced thoracic radiologist (L.J.M.K.), who was blinded to the original CT report, the location of the filling defect, and the clinical information of the patients. Both the degree of pulmonary artery obstruction, according to the scoring system of Qanadli, and the largest pulmonary artery involved, i.e. central or interlobar, segmental, or subsegmental, were assessed. The Qanadli obstruction index was defined as the number of segmental artery branches that are blocked, with one point assigned for partial blockage, or two points for complete obstructive PE. With this scoring system, 40 is the highest possible score, corresponding to a 100% obstruction index [4]. To compare the obstruction indexes of patients with incidental PE with those of patients with symptomatic PE, we used a previously described cohort of 113 consecutive patients with acute symptomatic PE diagnosed on CT pulmonary angiography (CTPA) as a reference group [2,5]. A retrospective chart review was performed to record the clinical outcome. All patients were followed for 6 months for the occurrence of death. The cause of mortality was assessed by reviewing the pathology report. In the cases in which an autopsy was not performed, the likely cause of death was verified with the treating physician by reviewing the medical records and death certificates. The obstruction indexes of patients with incidental and symptomatic PE were compared for statistical difference with the Mann–Whitney test. Cox regression analyses were performed to assess the impact of the level of obstruction on survival during 6 months of follow-up. The hazard ratio (HR) was adjusted for potential confounders, including age, gender, and stage of the malignancy (i.e. localized vs. metastatic). SPSS version 20 (SPSS, Chicago, IL, USA) was used for all analyses. During the study period, incidental PE was diagnosed in a total of 65 patients. The original CT images could Correspondence: Paul den Exter, Department of Thrombosis and Hemostasis, Leiden University Medical Center C7-68, Albinusdreef 2, P.O Box 9600, 2300 RC, Leiden, the Netherlands. Tel.: + 31 71 526 2085; fax: +31 71 524 8140. E-mail: p.l.den_exter@lumc.nl

Is a normal computed tomography pulmonary angiography safe to rule out acute pulmonary embolism in patients with a likely clinical probability

A normal computed tomography pulmonary angiography (CTPA) remains a controversial criterion for ruling out acute pulmonary embolism (PE) in patients with a likely clinical probability. We set out to determine the risk of VTE and fatal PE after a normal CTPA in this patient category and compare these risk to those after a normal pulmonary angiogram of 1.7u2009% (95u2009%CI 1.0-2.7u2009%) and 0.3u2009% (95u2009%CI 0.02-0.7u2009%). A patient-level meta-analysis from 4 prospective diagnostic management studies that sequentially applied the Wells rule, D-dimer tests and CTPA to consecutive patients with clinically suspected acute PE. The primary outcome was the 3-month VTE incidence after a normal CTPA. A total of 6,148 patients were included with an overall PE prevalence of 24u2009%. The 3-month VTE incidence in all 4,421 patients in whom PE was excluded at baseline was 1.2u2009% (95u2009%CI 0.48-2.6) and the risk of fatal PE was 0.11u2009% (95u2009%CI 0.02-0.70). In patients with a likely clinical probability the 3-month incidences of VTE and fatal PE were 2.0u2009% (95u2009%CI 1.0-4.1u2009%) and 0.48u2009% (95u2009%CI 0.20-1.1u2009%) after a normal CTPA. The 3-month incidence of VTE was 6.3u2009% (95u2009%CI 3.0-12) in patients with a Wells rule >6 points. In conclusion, this study suggests that a normal CTPA may be considered as a valid diagnostic criterion to rule out PE in the majority of patients with a likely clinical probability, although the risk of VTE is higher in subgroups such as patients with a Wells rule >6 points for which a closer follow-up should be considered.

Is stand-alone D-dimer testing safe to rule out acute pulmonary embolism?

Essentials A stand‐alone D‐dimer below 750 μg/L has been proposed to rule out acute pulmonary embolism (PE). This was a post‐hoc analysis on data from 6 studies comprising 7268 patients with suspected PE. The negative predictive value of a D‐dimer <750 μg/L ranged from 79% to 96% in various subgroups. Stand‐alone D‐dimer testing seems to be unsafe to rule out PE in all patients.

No added value of the age-adjusted D-dimer cut-off to the YEARS algorithm in patients with suspected pulmonary embolism

Essentials Imaging is warranted in the majority of patients to confirm or rule out pulmonary embolism (PE). The age‐adjusted D‐dimer (ADJUST) reduced the number of required imaging tests in patients ≥ 50 years. The YEARS algorithm was designed to improve the efficiency in patients with suspected PE. There was no added value of implementing ADJUST in the YEARS algorithm in our cohort.

Combination of Pulmonary Embolism Rule-out Criteria and YEARS Algorithm in a European Cohort of Patients with Suspected Pulmonary Embolism

BACKGROUNDnBoth the YEARS algorithm and the pulmonary embolism (PE) rule-out criteria (PERC) were created to exclude PE with limited diagnostic tests. A diagnostic strategy combining both scores might save additional computed tomography pulmonary angiography (CTPA) scans, but they have never been evaluated in conjunction.nnnAIMnThe aim of this study was to determine the safety and efficiency of combining YEARS and PERC in a single diagnostic strategy for suspected PE.nnnMETHODSnThe PERC rule was assessed in 1,316 consecutive patients with suspected PE who were managed according to YEARS. We calculated the absolute difference (with 95% confidence interval [CI]) in failure rate and the number of saved CTPAs for the scenario that PE would have been ruled out without CTPA in the absence of all PERC items.nnnRESULTSnUsing the YEARS algorithm, PE was diagnosed in 189 patients (14%), 680 patients (52%) were managed without CTPA and the 3-month rate of venous thromboembolism in patients in whom PE was ruled out was 0.44% (95% CI: 0.19-1.0). Only 6 of 154 patients (3.9%; 95% CI: 1.4-8.2) with no YEARS items who were referred for CTPA would have been PERC negative, of whom none were diagnosed with PE at baseline or during follow-up (0%; 95% CI: 0-64). Applying PERC before YEARS in all patients would have led to a failure rate of 1.42% (95% CI: 0.87-2.3%), 0.98% (95% CI: 0.17-1.9) more than shown in patients managed by YEARS.nnnCONCLUSIONnCombining YEARS with PERC would have yielded only a modest improvement of efficiency in patients without a YEARS item and an unacceptable failure rate in patients with ≥u20091 YEARS item.

Sex-specific performance of pre-imaging diagnostic algorithms for pulmonary embolism

Essentials Decision rules for pulmonary embolism are used indiscriminately despite possible sex‐differences. Various pre‐imaging diagnostic algorithms have been investigated in several prospective studies. When analysed at an individual patient data level the algorithms perform similarly in both sexes. Estrogen use and male sex were associated with a higher prevalence in suspected pulmonary embolism.