Endothelin is not elevated in acute pulmonary embolism

Introduction

In acute pulmonary embolism (APE) the increase of pulmonary vascular resistance depends on the thromboli load and potentially on the pulmonary bed contraction caused by neurohormonal reaction. Plasma levels of endothelin were reported to be elevated in pulmonary arterial hypertension. However, there are only a few studies assessing endothelin in patients with APE.

Materials & Methods

Therefore in our study we evaluated endothelin concentration in 55 patients (29M, 26F, age 57 ± 19 yrs) with confirmed APE for potential value in risk stratification. Patients were compared with 24 healthy volunteers at similar age. On admission blood samples were collected for plasma endothelin concentration. The quantitative assessment of right ventricular (RV) function was performed by echocardiography.

Results

Endothelin concentrations were similar in APE patients and in control group (1.41(0.22-9.68)pg/mL vs. 1.62(0.27-8.92)pg/mL; p = NS). There was no differences in endothelin levels between APE patients with and without RV dysfunction (1.46(0.38-4.54)pg/mL vs. 1.41(0.22-9.68)pg/mL; p = NS). Endothelin concentration did not differ between patients with serious adverse events and APE group with event-free clinical course (3.19(0.38-4.27)pg/mL vs. 1.38(0.22-9.68)pg/mL; p = NS). There was no significant correlation between endothelin levels and blood saturation, time from the first symptoms, heart rate, blood pressure, tricuspid valve regurgitation pressure gradient and other echocardiographic parameters.

Conclusions

We concluded that plasma endothelin concentrations assessed on admission are not elevated in patients with APE and it does not play as important role in acute phase of increase of pressure in pulmonary arteries as in chronic pulmonary hypertension.     

Active search for chronic thromboembolic pulmonary hypertension does not appear indicated after acute pulmonary embolism

Introduction

Chronic thromboembolic pulmonary hypertension (CTEPH) is a life threatening but often, by pulmonary endarterectomy, curable disease. The incidence of CTEPH after an acute pulmonary embolism (PE) appears to be much higher than previously thought. Systematic follow-up of patients after PE might increase the number of diagnosed CTEPH patients.

Aim

To study whether, compared to current clinical practice, a systematic search for CTEPH in patients after acute PE would increase the number of patients diagnosed with symptomatic, potentially treatable CTEPH.

Methods

Consecutive patients with a prior diagnosis of acute PE were presented with a questionnaire, designed to establish the presence of either new or worsened dyspnea after the acute PE episode. If so, patients were evaluated for the presence of CTEPH.

Results

PE patients (n = 110; 56 ± 18 years) were included after a median follow-up of three years. Overall mortality was 34% (37 patients); 1 patient had died due to CTEPH.In total 62 out of 69 questionnaires were returned; 23 patients reported new or worsened dyspnea related to the PE episode, and qualified for additional testing. In 2 patients, CTEPH was already diagnosed prior to this study. None of the remaining patients met the criteria for the diagnosis of CTEPH. The overall incidence of 2.7% (3/110; 95%CI 0.6-7.8%) is in agreement with earlier reported incidences.

Conclusion

Our findings do not point to a role for a systematic search and pro-active approach towards patients with a recent history of pulmonary embolism to increase the number of patients diagnosed with potentially treatable CTEPH.     

Extracorporeal cardiopulmonary support may be an efficient rescue of patients after massive pulmonary embolism. An experimental porcine study

Introduction

Treatment of massive pulmonary embolism leading to cardiac arrest is controversial but restitution of circulation within a shorter time is crucial. Cardiopulmonary support and therapeutic hypothermia is an option for cardiac arrest and could be used to treat massive PE. However, hypothermia may influence the effect of the ongoing intrinsic fibrinolysis.

Objectives

To establish a porcine model of massive pulmonary embolism, to show that cardiopulmonary support can rescue pigs with massive pulmonary embolism and to examine the effect of hypothermia on fibrinolysis.

Methods

Pigs ~ 80 kg were anesthetised and prepared for cardiopulmonary support. Repetitive injections of preformed blood thrombi into the right atrium were done until cardiac arrest. Cardiopulmonary support was established and eighteen pigs were randomised into 3 groups: Normothermia (38-39 °C); hypothermia (33-34 °C); or medication with recombinant tissue plasminogen activator. After three hours the pigs were weaned from cardiopulmonary support, and after 15 minutes with spontaneous circulation assassinated and autopsied. Remaining thrombi in the lungs were weighed.

Results

The development of fatal pulmonary embolism was highly reproducible. All 18 pigs could be weaned from cardiopulmonary support and survived more than 15 minutes. The amount of remaining thromboemboli was substantial in all groups and not significantly different between groups. Normothermic group 20.0 ± 2.2 g, Hypothermic group 17.0 ± 3.7 g, and rt-PA group 14.3 ± 3.2 g.

Conclusions

Cardiopulmonary support could rescue pigs with massive pulmonary embolism. Hypothermia did not reduce the emboli but may for other reasons be beneficial. The optimal additional treatment is still unknown but treatment modalities can be tested in this model.     

Right ventricular dysfunction in hemodynamically stable patients with acute pulmonary embolism

Background

Echocardiography for risk stratification in hemodynamically stable patients with pulmonary embolism (PE) is well-established. Right ventricular dysfunction (RVD) is associated with an elevated mortality and adverse outcome. The aim of our study was to compare RVD criteria and investigate the role of elevated systolic pulmonary artery pressure (sPAP) in the diagnosis of RVD.

Methods

We retrospectively analyzed the echocardiographic and laboratory data of all hemodynamically stable patients with confirmed PE (2006-2011). The data were compared with three different definitions of RVD: Definition 1: RV dilatation, abnormal motion of interventricular septum, RV hypokinesis or tricuspid regurgitation. Definition 2: as with definition 1 but including elevated sPAP (> 30 mmHg). Definition 3: elevated sPAP (> 30 mmHg) as single RVD criterion.

Results

A total number of 129 patients (59.7% women, age 70.0 years (60.7/81.0)) were included in this study. Median Troponin I level was measured as 0.02 ng/ml (0/0.14); mean sPAP 33.9 ± 18.5 mmHg. The troponin cut-off levels for predicting a RVD of the 3 RVD definitions were in definition 1-3: > 0.01 ng/ml, > 0.01 ng/ml and > 0.00 ng/ml. Analysis of the ROC curve showed an AUC for RVD definitions 1-3: 0.790, 0.796 and 0.635.

Conclusions

The combination of commonly used RVD criteria with added elevated sPAP improves the diagnosis of RVD in acute PE. Troponin I values of > 0.01 ng/ml in acute PE point to an RVD.     

Quality of individual INR control and the risk of stroke and bleeding events in atrial fibrillation patients: a nested case control analysis of the ACTIVE W study

Introduction

Time in therapeutic range (TTR) for international normalized ratio (INR) is an accepted quality measure of anticoagulation control in patient populations, but its usefulness for predicting stroke and bleeding in individuals is not well understood.

Materials and Methods

In a nested case control analysis among ACTIVE W study patients, cases with stroke and cases with bleeding were separately matched with controls. Several anticoagulation quality measures were compared, overall and in a time-dependent manner.

Results

32 cases with ischemic stroke and 234 cases with bleeding in the analysis were matched in a 4:1 ratio to 122 and 865 controls, respectively. Follow-up duration was 257 ± 154 days for the stroke analysis and 222 ± 146 days for the bleeding analysis. Compared with their respective controls, the study mean TTR of both stroke cases (53.9% ± 25.1 vs 63.4% ± 24.8; p = 0.055) and bleeding cases (56.2% ± 25.4 vs 63.4% ± 26.8; p < 0.001) was lower. Time below range for stroke and time above range for bleeding were only greater in the last month leading up to the event, not over the entire study period. Rather, over the entire study period bleeding cases spent more time below range than controls (26.8% ± 25.9 vs 20.8% ± 24.0; p = 0.001).

Conclusions

TTR was lower in individual AF patients with stroke or bleeding compared with matched controls in ACTIVE W. Maintaining a high TTR, with equal importance to avoid low and high INRs, is a relevant goal of individual patient treatment to prevent stroke and bleeding.     

Bolus tenecteplase for right ventricle dysfunction in hemodynamically stable patients with pulmonary embolism

Introduction

The clinical benefit of thrombolytic treatment over heparin in patients with pulmonary embolism without hemodynamic compromise remains controversial. In these patients bolus tenecteplase has the potential to provide an effective and safe thrombolysis.

Methods

We evaluated the effect of tenecteplase on right ventricle dysfunction (RVD) assessed by echocardiography in hemodynamically stable patients with PE in a multicenter, randomized, double-blind, placebo-controlled study. RVD was defined as right/left ventricle end-diastolic dimension ratio > 1 in the apical 4-chamber view. Patients were randomized to receive weight-adjusted single-bolus tenecteplase or placebo. All patients received unfractionated heparin. Reduction of RVD at 24 hours was the primary efficacy end-point and was evaluated by an independent committee unaware of treatment allocation.

Results

Overall, 58 patients were randomized. Echocardiograms were adequate for efficacy analysis in 51 patients, 23 randomized to tenecteplase and 28 to placebo. The reduction of right to left ventricle end-diastolic dimension ratio at 24 hours was 0.31 ± 0.08 in patients randomized to tenecteplase as compared to 0.10 ± 0.07 in patients randomized to placebo (p = 0.04). One patient randomized to tenecteplase suffered a clinical event (recurrent pulmonary embolism) in comparison to three patients randomized to placebo (1 recurrent pulmonary embolism; 1 clinical deterioration and 1 non pulmonary embolism-related death). Two non fatal major bleedings occurred with tenecteplase (1 intracranial) and one with placebo.

Conclusion

In hemodynamically stable patients with PE, treatment with single bolus tenecteplase is feasible at the same dosages used for acute myocardial infarction and is associated with reduction of RVD at 24 hours. Whether this benefit is associated with an improved clinical outcome without excessive bleeding is currently explored in a large clinical trial.     

Inefficient exercise gas exchange identifies pulmonary hypertension in chronic thromboembolic obstruction following pulmonary embolism

Introduction

Persistent obstruction in the pulmonary artery following acute pulmonary embolism (PE) can give rise to both chronic thromboembolic pulmonary hypertension (CTEPH) and chronic thromboembolic disease without PH (CTED). We hypothesised that cardiopulmonary exercise testing (CPET) may be able to differentiate patients with CTEPH and CTED following unresolved PE which may help guide patient assessment.

Materials and Methods

Fifteen patients with CTEPH and 15 with CTED all diagnosed after PE underwent CT pulmonary angiography, CPET and resting right heart catheterisation. Exercise variables were compared between patients with CTEPH, CTED and 10 sedentary controls and analysed as predictors of a CTEPH diagnosis. Proximal thrombotic burden in CTEPH and CTED was quantified using CT criteria.

Results

Physiological dead space (Vd/Vt) (34.5 ± 11.4 vs 50.8 ± 6.6 %, p < 0.001) and alveolar-arterial oxygen gradient (29 ± 16 vs 46 ± 12 mmHg, p < 0.001) at peak exercise strongly differentiated CTED and CTEPH groups respectively. Resting ventilatory efficiency also differed from control subjects. In both univariate and multivariate analyses, peak exercise Vd/Vt predicted a diagnosis of CTEPH (ROC AUC > 0.88, 0.67 - 0.97) despite a similar degree of proximal thrombotic obstruction to the CTED group (67.5, 55 - 70% and 72.5, 60 - 80% respectively, p = 0.08).

Conclusions

Gas exchange at peak exercise differentiates CTED and CTEPH after PE that can present with no apparent relation to the degree of proximal thrombotic burden. A potential role for CPET exists in guiding further clinical investigations in this setting.     

Plasma homocysteine level and left ventricular thrombus formation in acute anterior myocardial infarction patients following thrombolytic therapy with t-PA

Aims

The aim of this study was to evaluate the relationship between homocysteine levels and the development of left ventricular thrombus in acute anterior myocardial infarction patients directed to thrombolytic therapy.

Methods and Results

Seventy-nine patients presenting with ST elevated acute anterior myocardial infarction and treated with thrombolytic agent, t-PA, were included in the study. Two-dimensional echocardiography was used to divide patients into 2 groups according to the presence (n = 14) or absence (n = 65) of thrombus in the left ventricle following myocardial infarction. The levels of fasting plasma total homocysteine, total cholesterol, triglycerides, HDL-cholesterol, LDL-cholesterol, vitamin B12 and folic acid were assessed. There were no significant differences between two groups in terms of age, gender, hyperlipidemia and smoking. History of diabetes mellitus (28.57% versus 6.15%, p = 0.04), peak creatine phosphokinase levels (4153.54 ± 1228.41 U/L versus 2456.92 ± 1421.36 U/L, p < 0.001), mean left ventricular wall motion score index (2.21 ± 0.18 versus 1.83 ± 0.23, p < 0.001) and total fasting homocysteine levels (18.24 ± 5.67 mmol/L versus 12.31 ± 3.52 mmol/L, p < 0.001) were significantly higher in patients with left ventricular thrombus. In multivariate analysis; only diabetes mellitus (p = 0.03), higher wall motion score index (p = 0.001) and higher homocysteine levels (p = 0.04) were independent predictors of left ventricular thrombus formation.

Conclusion

Our results suggest that; diabetes mellitus, higher wall motion score index and hyperhomocysteinemia independently increases the risk for the development of left ventricular thrombus formation in patients with acute anterior myocardial infarction following thrombolytic therapy.     

Central thromboembolism is a possible predictor of right heart dysfunction in normotensive patients with acute pulmonary embolism

Background

Right heart dysfunction is a crucial factor in risk stratification of normotensive patients with pulmonary embolism. Apart from biomarkers, determinants of right heart dysfunction in this group of patients are not yet well established.

Aim and method

In order to identify such determinants, we analysed data of 252 patients with acute pulmonary embolism admitted to our hospital in 2008.

Results

69 out of 140 patients showed right heart dysfunction by echocardiography within 24 hours after diagnosis, 71 did not. Right ventricular dysfunction was significantly more frequent in patients with central clots on computed tomography (p = 0.004), a history of syncope (p < 0.001) and among women on oral contraceptives (p = 0.003). In multiple regression analysis, only central thromboembolism (p < 0.001) was identified as individual predictor of right ventricular dysfunction. Age, gender, body mass index, idiopathic or recurrent thromboembolism, duration of symptoms, preceding surgery, room air oxygen saturation, carcinoma, hypertension, diabetes, renal disease, congestive left heart failure and concomitant lung disease were equally distributed. In comparison with NT-pro brain natriuretic peptide (PPV 67%, NPV 75%, p = 0.782) and troponin I (PPV 76%, NPV 62%, p = 0.336), central thromboembolism has shown to have a greater statistical power in predicting right heart dysfunction in normotensive patients with pulmonary embolism (PPV 78%, NPV 88%, p < 0.001).

Conclusion

Among normotensive patients with acute pulmonary embolism, those with central clots seem to be at greater risk for echocardiographically evaluated right ventricular dysfunction.     

Testing for occult cancer in patients with pulmonary embolism: Results from a screening program and a two-year follow-up survey

Introduction

An association between pulmonary embolism (PE) and a subsequent diagnosis of cancer has been repeatedly reported. Although screening and early detection might play a pivotal part in reducing mortality from cancer, there are currently no definite data to suggest that cancer screening may improve survival rates in patients with PE. We hereby present the results of a screening program and a two-year follow-up survey for detecting occult cancer in this patient population.

Materials and methods

A total of 107 patients with PE were consecutively enrolled. All subjects underwent an initial screening program followed by a two-year follow-up survey. We calculated the sensitivity of our screening program, and identified risk factors associated with occult cancer by means of logistic regression.

Results

The initial screening program yielded positive results in five patients (4.7%), and four additional cases were identified during the 2-year follow-up. The overall sensitivity of our screening program in idiopathic PE was 55.5%. In the entire study cohort, the number necessary for screening was 12.1 (6.1 in idiopathic PE, and 58 in secondary PE). Logistic regression analysis revealed that a shock index ≥ 1 (odds ratio: 5.467; p = 0.007) and idiopathic PE (odds ratio: 12.82; p = 0.03) were independent risk factors for occult cancer in our PE patients.

Conclusions

A simple and noninvasive screening program yields an acceptable sensitivity for detecting occult cancer in idiopathic PE patients. These results highlight the importance of screening for occult cancer in patients diagnosed with PE, especially in idiopathic forms.     

Changes in plasma von Willebrand factor and ADAMTS13 levels associated with left atrial remodeling in atrial fibrillation

Introduction

Previous studies have shown raised plasma von Willebrand factor (VWF) levels in patients with atrial fibrillation (AF). However, little is known about changes of VWF associated with VWF-cleaving protease (ADAMTS13) in AF. The aim of this study was to examine the relationship between changes in plasma VWF and ADAMTS13 levels, and left atrial remodeling in AF patients.

Materials and Methods

We measured plasma VWF and ADAMTS13 antigen levels in 70 paroxysmal AF (PAF) patients, 56 chronic AF (CAF) patients, and 55 control subjects.

Results

Plasma VWF levels (mU/ml) were significantly higher in CAF and PAF patients compared with the controls (2103 ± 743, 1930 ± 676, 1532 ± 555, respectively, P < 0.0001 in CAF vs. controls, P = 0.001 in PAF vs. control), while ADAMTS13 levels (mU/ml) were significantly lower in CAF and PAF patients compared with the controls (795 ± 169, 860 ± 221, 932 ± 173, respectively, P = 0.0002 in CAF vs. controls, P = 0.04 in PAF vs. control). The VWF/ADAMTS13 ratio was significantly higher in patients with CAF than PAF or controls (2.81 ± 1.30, 2.34 ± 0.92, 1.73 ± 0.83, respectively; P = 0.01 in CAF vs. PAF, P < 0.0001 in CAF vs. controls). There was a significant correlation between the VWF/ADAMTS13 ratio and left atrial diameter (positive correlation; r = 0.275, P = 0.0002) and left atrial appendage flow velocity (negative correlation; r = - 0.345, P = 0.0018).

Conclusions

These findings suggest that the imbalance between plasma VWF and ADAMTS13 levels caused by left atrial remodeling might be closely associated with intra-atrial thrombus formation in AF patients.     

Microvascular obstruction in the right ventricle in reperfused anterior myocardial infarction. Macroscopic and pathologic evidence in a swine model

Introduction

Data on right ventricular (RV) involvement in anterior myocardial infarction are scarce. The presence of RV microvascular obstruction (MVO) in this context has not been analyzed yet. The aim of the present study was to characterize the presence of MVO in the RV in a controlled experimental swine model of reperfused anterior myocardial infarction.

Materials and Methods

Left anterior descending (LAD) artery-perfused area (thioflavin-S staining after selective infusion in LAD artery), infarct size (lack of triphenyltetrazolium-chloride staining) and MVO (lack of thioflavin-S staining in the core of the infarcted area) in the RV were studied. A quantitative (% of the ventricular volume) and semiquantitative (number of segments involved) analysis was carried out both in the RV and LV in a 90-min left anterior descending balloon occlusion and 3-day reperfusion model in swine (n = 15).

Results

RV infarction and RV MVO (> 1 segment) were detected in 9 (60%) and 6 (40%) cases respectively. Mean LAD-perfused area, infarct size and MVO in the RV were 33.8 ± 13%, 13.53 ± 11.7% and 3.4 ± 4.5%. Haematoxylin and eosin stains and electron microscopy of the RV-MVO areas demonstrated generalized cardiomyocyte necrosis and inflammatory infiltration along with patched hemorrhagic areas. Ex-vivo nuclear magnetic resonance (T2* sequences) microimaging of RV-MVO showed, in comparison with remote non-infarcted territories, marked hypointense zones (corresponding to necrosis, inflammation and hemorrhage) in the core of hyperintense regions (corresponding to edema).

Conclusions

In reperfused anterior myocardial infarction, MVO is frequently present in the RV. It is associated with severe histologic repercussion on the RV wall. Nuclear magnetic resonance appears as a promising technique for the noninvasive detection of this phenomenon. Further studies are warranted to evaluate the pathophysiological and clinical implications.     

Increased thrombin generation in inflammatory bowel diseases

Background

Inflammatory bowel diseases (IBD) are characterized by an increased thrombotic risk of uncertain etiology. Endogenous thrombin potential (ETP), a parameter of the thrombin generation curve, represents a new tool in the evaluation of thrombotic and bleeding disorders.

Aims

To study ETP in IBD patients and to correlate the results with clinical and biochemical features.

Methods

Seventy-four IBD patients (37 ulcerative colitis and 37 Crohn's disease) and 74 sex- and age-matched healthy individuals. ETP was measured upon activation of coagulation with small amounts of tissue factor and phospholipids in the presence or absence of thrombomodulin; results were expressed as nM thrombin·minutes.

Results

Mean±SD ETP values were significantly higher in patients (1,499 ± 454) than controls (1,261 ± 385) (p < 0.001) only when the test was performed in the presence of thrombomodulin. ETP evaluated as ratio (with/without thrombomodulin), taken as an index of hypercoagulability, was significantly higher in patients (0.69 ± 0.14) than controls (0.62 ± 0.18) (p < 0.006). Patients with increased C-reactive protein (CRP) had significantly higher mean ETP (1,721 ± 458) than those with normal CRP (1,357 ± 394) or controls (1,261 ± 385) (p < 0.001). Patients who at the time of blood sampling were classified as having a clinically active disease had ETP higher than those who were quiescent (1,655 ± 451 versus 1,388 ± 427, p < 0.001) or controls (1,261 ± 385, p < 0.001).

Conclusions

ETP measured in the presence of thrombomodulin or as ratio (with/without thrombomodulin) is increased in IBD patients, mainly in those with increased CRP or active disease. It may be considered as a candidate test for prospective studies aimed at assessing the risk of thrombosis in IBD patients.     

Prognostic implications of computed tomographic right ventricular dilation in patients with acute pulmonary embolism

Introduction

Whether right ventricular (RV) dilation on computerized tomography (RVD-CT) is a useful predictor for clinical outcomes of acute pulmonary embolism (PE) remains debatable. Furthermore, data regarding the best combination of prognostic markers for predicting the adverse outcome of PE are limited.

Materials and Methods

The authors retrospectively reviewed 657 consecutive patients hospitalized at a tertiary referral center with a diagnosis of PE based on multi-detector row CT scan.

Results

Patients were allocated into an adverse outcome group (11% [n = 69]) or a low risk group (89% [n = 588]). Multivariate analysis showed that RVD-CT (RV/left ventricle [LV] diameter ratio ≥ 1), high pulmonary embolism severity index (PESI) score (class IV-V), high N-terminal-pro-B-type natriuretic peptide (NT-proBNP,≥1,136 pg/ml), and elevated troponin I (≥ 0.05 ng/ml) significantly predicted an adverse outcome (odds ratio [OR] 6.26, 95% confidence interval [CI] 2.74-14.31, p < 0.001; OR 4.71, 95% CI 2.00-11.07, p < 0.001; OR 2.71, 95% CI 1.15-6.39, p = 0.023; and OR 3.00, 95% CI 1.27-7.07, p = 0.012, respectively). The addition of RVD-CT to PESI, NT-proBNP, troponin I or their combinations enhanced the positive predictive values and positive likelihood ratios of an adverse outcome.

Conclusions

RVD-CT could be an independent prognostic factor of adverse outcomes in patients with acute PE, and provides additional prognostic value when combined with other prognostic factors.     

Does the Pulmonary Embolism Severity Index accurately identify low risk patients eligible for outpatient treatment?

Introduction

The pulmonary embolism severity index (PESI) and the recently derived simplified PESI prognostic model have been developed to estimate the risk of 30-day mortality in patients with acute PE. We sought to assess if the PESI and simplified PESI prognostic models can accurately identify adverse events and to determine the rates of events in patients treated as outpatients.

Methods

A retrospective cohort study of patients with acute pulmonary embolism (PE) presenting at the Ottawa Hospital (Canada) was conducted between 1 January 2007 and 31 December 2008.

Results

Two hundred and forty three patients were included. A total of 118 (48.6%) and 81 (33.3%) were classified as low risk patients using the original and simplified PESI prognostic models respectively. None of the low risk patients died within the 3 months of follow-up. One hundred and fifteen (47.3%) patients were safely treated as outpatients with no deaths or bleeding episodes and only 1 recurrent event within the first 14 days or after 30 days of follow-up. Thirty four (29.6%) of these outpatients were classified as high risk patients according to the original PESI and 54 (47.0%) to the simplified PESI prognostic model.

Conclusion

Both PESI strategies accurately identify patients with acute PE who are at low risk and high risk for short-term adverse events. However, 30 to 47% of patients with acute PE and a high risk PESI score were safely managed as outpatients. Future research should be directed at developing tools that predict which patients would benefit from inpatient management.     

Comparison of the clinical usefulness of two quantitative D-Dimer tests in patients with a low clinical probability of pulmonary embolism

Background

Quantitative D-Dimer tests are established methods in the non-invasive diagnostic management to rule out venous thromboembolism (VTE). The diagnostic performance and the clinical efficiency different D-Dimer assays in the exclusion of pulmonary embolism (PE) have not yet been compared in a clinical outcome study.

Objective

Evaluation of the efficiency and safety of excluding the diagnosis of PE with two different quantitative D-Dimer assays in consecutive patients with clinically suspected PE.

Patients and Methods

We studied the VTE-failure rate of 2206 consecutive patients with an unlikely clinical probability in whom VIDAS or Tinaquant D-Dimer tests were performed.

Results

The prevalence of PE in 1238 patients whose D-Dimer level was analyzed with Tinaquant assay was 11%. The VIDAS assay group consisted of 968 patients with a PE prevalence of 13%. The VIDAS assay had a sensitivity of 99.2% (95%CI; 96- > 99.9%), the Tinaquant assay of 97.3% (95%CI; 93 -99%). The negative predictive value (NPV) in the Tinaquant assay group was 99.4% (95%CI 98-99.8%) in comparison to 99.7% (95%CI 99-> 99.9%) in the VIDAS assay group. During 3 month of follow-up, there were no fatal cases of PE among patients with normal D-Dimer and unlikely clinical probability in both D-Dimer assay groups. In addition, the test efficiency of Tinaquant assay was significantly higher in comparison to VIDAS assay (52% vs 42%, p < 0.001).

Conclusion

Both Tinaquant and VIDAS D-Dimer tests perform equally well in combination with an unlikely clinical probability in excluding PE. The Tinaquant test was shown to be more efficient.     

Echocardiographic assessment of pulmonary arterial pressure in the follow-up of patients with pulmonary embolism

Background

Echocardiography remains a clinically useful screening test for chronic thromboembolic pulmonary hypertension (CTEPH) in patients with a history of pulmonary embolism (PE). To devise an effective screening strategy, the definition of a high-risk group is necessary.

Methods

We examined a total of 744 patients with acute symptomatic pulmonary embolism (PE) who were enrolled in a Spanish multicenter study. Patients were monitored every 6 months during the first two years, and then once a year thereafter. Transthoracic echocardiography was used to screen patients with a clinical suspicion of CTEPH during follow-up. Pulmonary arterial hypertension was defined as an estimated pulmonary artery systolic pressure (PAP) > 50 mm Hg. The index thromboembolic episode was considered severe if: (a) the patient was immobilized for medical reasons; or (b) systolic blood pressure was less than 90 mm Hg; or (c) troponin T values were above the reference range.

Results

The incidence of PAP > 50 mm Hg at 36 months was 8.3% (95% confidence interval = 4.6%-14.5%). Statistical analysis showed a highly significant association between a severe index thromboembolic episode and the subsequent detection of PAP > 50 mm Hg on echocardiography, with high positive likelihood ratio (2.40) and negative predictive value (> 0.97).

Conclusions

Patients with a severe index thromboembolic episode would constitute a high-risk group for the development of CTEPH. This group of patients should be subjected to a strict follow-up protocol.     

Patients with primary antiphospholipid antibody syndrome and without associated vascular risk factors present a normal endothelial function

Introduction

Primary antiphospholipid antibody syndrome (PAPS) is characterized by venous or arterial thrombosis and positive antiphospholipid antibodies. It is controversial whether PAPS patients have early atherosclerosis. Endothelial dysfunction is an early event in the natural history of atherosclerosis. Aim of our study was to compare endothelial function of patients with PAPS and no associated risk factors with that of age- and sex-matched controls.

Materials and Methods

Patients with PAPS, carefully selected to exclude all known risk factors for cardiovascular diseases, estrogen therapy, pregnancy, intake of drugs affecting endothelial function, vitamins or antioxidants, were included in a case-control study. Controls were age- (± 5 years) and sex-matched subjects with the same exclusion criteria but without PAPS. Flow-mediated dilation of the brachial artery and some plasmatic markers of endothelial and platelet activation were measured. Measures are expressed as mean±SEM.

Results

Twenty cases (mean age 42 ± 4.0 years, 11 females) and 39 controls (mean age 41 ± 2.9, 22 females) were studied. FMD was 5.7 ± 0.8% in cases (95% CI: 4.1 to 7.3) and 6.8 ± 0.5% (5.7 to 7.9) in controls (p = NS). Plasma von Willebrand factor was 128 ± 11.3% and 134.2 ± 16.1% in cases and controls, respectively (p = NS). Soluble P-selectin and soluble CD40L were 94.1 ± 4.9 ng/ml and 0.7 ± 0.1 ng/ml in cases and 87.7 ± 4.0 ng/ml and 1.0 ± 0.2 in controls, respectively (p = NS). In a substudy, circulating progenitor and mature endothelial cells were comparable between the two groups.

Conclusions

Endothelial function in patients with PAPS and no associated risk factors is similar to that of age- and sex- matched controls. These data suggest that the alterations leading to thrombosis in PAPS concern primarily the clotting system.     

Clinical prediction of pulmonary embolism in respiratory emergencies

Introduction

The initial management of suspected pulmonary embolism (PE) is commonly done in respiratory departments, but is based on clinical prediction rules developed in other settings.

Objective

To determine the accuracy of established prediction rules for PE in patients with respiratory emergencies.

Design

A prospective study

Materials and Methods

Patients presenting to respiratory emergency department with acute symptoms and signs suggestive of PE (n = 183) and subsequently admitted to hospital were prospectively enrolled. Wells’ rule, original and revised Geneva scores, their components separately, and other common clinical parameters were recorded during admission. PE was diagnosed by perfusion lung scanning, computed tomographic pulmonary angiography, lower limb venous ultrasonography, magnetic resonance pulmonary angiography, and/or pulmonary angiography.

Results

PE was confirmed in 52 and ruled out in 131 patients. Tachycardia, atelectasis, elevated hemidiaphragm, clinical signs of deep-venous thrombosis, physician perception that PE is the likeliest diagnosis, previous thromboembolism, chest pain, and absence of chronic obstructive pulmonary disease or cough were associated with the presence of PE. These significant parameters could be combined for accurate pre-test PE prediction, with a newly devised combinatorial tool exhibiting the highest area under curve [0.92 (95% CI: 0.87-0.97)], followed by Wells’ rule [0.86 (95% CI 0.79-0.92)], the revised Geneva score [0.83 (95% CI 0.77-0.90)], and the original Geneva score [0.75 (95% CI 0.68-0.83)].

Conclusion

Wells’ rule and the revised Geneva score are more useful in diagnosing PE in respiratory emergencies. A newly devised prediction tool can be of even greater accuracy in this patient population.     

Efficacy and safety of enoxaparin in Japanese patients undergoing curative abdominal or pelvic cancer surgery: Results from a multicenter, randomized, open-label study

Background

Enoxaparin sodium (enoxaparin) is used worldwide for the prevention of venous thromboembolism (VTE). Registration trials of enoxaparin have been conducted primarily in Caucasian populations, and its preventive use in Japanese patients has yet to be established. To address this, we evaluated the efficacy and safety of postoperative enoxaparin in Japanese patients undergoing surgery for abdominal cancer.

Methods

This multicenter, open-label study randomized 151 Japanese patients undergoing curative surgery for abdominal cancer to enoxaparin 20 mg twice daily for 14 days, started 24-36 hours after surgery (n = 113) or intermittent pneumatic compression (IPC) as a reference (n = 38). IPC was performed at least once in both groups between randomization and surgery. The primary efficacy endpoint was the incidence of VTE in the modified intention-to-treat (mITT) population. The primary safety outcome was the incidence of any bleeding during treatment and follow-up.

Results

Incidence of VTE was 1.2% (95% CI, 0.03-6.53%) (1/83 patients) in the enoxaparin group and 19.4% (95% CI, 7.45-37.47%) (6/31 patients) in the IPC group. In the safety population, 10/109 patients in the enoxaparin group (9.2%; 95% CI, 4.49-16.23%) and 3/38 patients in the IPC group (7.9%; 95% CI, 1.66-21.38%) experienced a bleeding event. There were no cases of fatal bleeding or bleeding into any critical organ.

Conclusions

These favorable efficacy and safety data support the use of enoxaparin (20 mg twice daily for 14 days started 24-36 hours after surgery) in Japanese patients undergoing abdominal or pelvic cancer surgery.