Maria Cristina Vedovati

Prognostic Value of Troponins in Acute Pulmonary Embolism A Meta-Analysis

Background— Whether elevated serum troponin levels identify patients with acute pulmonary embolism at high risk of short-term mortality or adverse outcome is undefined. Methods and Results— We performed a meta-analysis of studies in patients with acute pulmonary embolism to assess the prognostic value of elevated troponin levels for short-term death and adverse outcome events (composite of death and any of the following: shock, need for thrombolysis, endotracheal intubation, catecholamine infusion, cardiopulmonary resuscitation, or recurrent pulmonary embolism). Unrestricted searches of MEDLINE and EMBASE bibliographic databases from January 1998 to November 2006 were performed using the terms “troponin” and “pulmonary embolism.” Additionally, review articles and bibliographies were manually searched. Cohort studies were included if they had used cardiac-specific troponin assays and had reported on short-term death or adverse outcome events. A random-effects model was used to pool study results; funnel-plot inspection was done to evaluate publication bias; and I2 testing was used to test for heterogeneity. Data from 20 studies (1985 patients) were included in the analysis. Overall, 122 of 618 patients with elevated troponin levels died (19.7%; 95% confidence interval [CI], 16.6 to 22.8) compared with 51 of 1367 with normal troponin levels (3.7%; 95% CI, 2.7 to 4.7). Elevated troponin levels were significantly associated with short-term mortality (odds ratio [OR], 5.24; 95% CI, 3.28 to 8.38), with death resulting from pulmonary embolism (OR, 9.44; 95% CI, 4.14 to 21.49), and with adverse outcome events (OR, 7.03; 95% CI, 2.42 to 20.43). Elevated troponin levels were associated with a high mortality in the subgroup of hemodynamically stable patients (OR, 5.90; 95% CI, 2.68 to 12.95). Results were consistent for troponin I or T and prospective or retrospective studies. Conclusions— Elevated troponin levels identify patients with acute pulmonary embolism at high risk of short-term death and adverse outcome events.

Direct Oral Anticoagulants in Patients With VTE and Cancer

BACKGROUNDnDirect oral anticoagulants (DOAs) have been shown to be as effective and at least as safe as conventional anticoagulation for the prevention of recurrences in patients with VTE. Whether this is the case in patients with cancer-associated VTE remains undefined.nnnMETHODSnWe performed a meta-analysis of randomized controlled trials with the aim of assessing the efficacy and safety of DOAs in patients with VTE and cancer. MEDLINE, EMBASE, and CENTRAL were searched up to December 2013 with no language restriction. The primary outcome of the analysis was recurrent VTE. Data on major bleeding (MB) and clinically relevant nonmajor bleeding were analyzed. Data were pooled and compared by ORs and 95% CIs.nnnRESULTSnOverall, 10 studies comparing DOAs with conventional anticoagulation for treatment of VTE including patients with cancer were included in the review. Six studies were included in the meta-analysis (two with dabigatran, two with rivaroxaban, one with edoxaban, and one with apixaban), accounting for a total of 1,132 patients. VTE recurred in 23 of 595 (3.9%) and in 32 of 537 (6.0%) patients with cancer treated with DOAs and conventional treatment, respectively (OR, 0.63; 95% CI, 0.37-1.10; I2, 0%). MB occurred in 3.2% and 4.2% of patients receiving DOAs and conventional treatment, respectively (OR, 0.77; 95% CI, 0.41-1.44; I2, 0%).nnnCONCLUSIONSnDOAs seem to be as effective and safe as conventional treatment for the prevention of VTE in patients with cancer. Further clinical trials in patients with cancer-associated VTE should be performed to confirm these results.

Multidetector computed tomography for acute pulmonary embolism: diagnosis and risk stratification in a single test

AIMSnIn patients with acute pulmonary embolism (PE), right ventricular dysfunction at echocardiography is associated with increased in-hospital mortality. The aims of this study in patients with acute PE were to identify a sensitive and simple criterion for right ventricular dysfunction at multidetector computed tomography (MDCT) using echocardiography as the reference standard and to evaluate the predictive value of the identified MDCT criterion for in-hospital death or clinical deterioration.nnnMETHODS AND RESULTSnRight ventricular dysfunction at MDCT was defined as the right-to-left ventricular dimensional ratio and was centrally assessed by a panel unaware of clinical and echocardiographic data. A right-to-left ventricular dimensional ratio ≥0.9 at MDCT had a 92% sensitivity for right ventricular dysfunction [95% confidence interval (CI) 88-96]. Overall, 457 patients were included in the outcome study: 303 had right ventricular dysfunction at MDCT. In-hospital death or clinical deterioration occurred in 44 patients with and in 8 patients without right ventricular dysfunction at MDCT (14.5 vs. 5.2%; P< 0.004). The negative predictive value of right ventricular dysfunction for death due to PE was 100% (95% CI 98-100). Right ventricular dysfunction at MDCT was an independent predictor for in-hospital death or clinical deterioration in the overall population [hazard ratio (HR) 3.5, 95% CI 1.6-7.7; P= 0.002] and in haemodynamically stable patients (HR 3.8, 95% CI 1.3-10.9; P= 0.007).nnnCONCLUSIONnIn patients with acute PE, MDCT might be used as a single procedure for diagnosis and risk stratification. Patients without right ventricular dysfunction at MDCT have a low risk of in-hospital adverse outcome.

Computed tomography to assess risk of death in acute pulmonary embolism: a meta-analysis

The aim of this study was to evaluate whether right ventricle dilation at computed tomography (CT) angiography can be used to assess the risk of death in patients with acute pulmonary embolism. Medline and EMBASE were searched up to April 30, 2013. Studies reporting on the association between right ventricle dilation (right-to-left ventricle diameter) or dysfunction (inter-ventricular septal bowing) at CT angiography and death at 30 days, as well as at 3 months in patients with acute pulmonary embolism, were included in a systematic review and meta-analysis. CT-detected right ventricle dilation was associated with an increased 30 day-mortality in all-comers with pulmonary embolism (OR 2.08 (95% CI 1.63–2.66); p<0.00001) and in haemodynamically stable patients (OR 1.64 (95% CI 1.06–2.52); p=0.03), as well as with death due to pulmonary embolism (OR 7.35 (95% CI 3.59–15.09); p<0.00001). An association between right ventricle dilation and 3-month mortality was also observed (OR 4.65 (95% CI 1.79–12.07); p=0.002). Right-to-left ventricle dilation as assessed by CT angiography can be used to evaluate risk of death in all-comers with pulmonary embolism and in haemodynamically stable patients. Multidetector CT can be used to assess short-term risk of death in patients with acute pulmonary embolism http://ow.ly/sNcBU

Incidence of arterial cardiovascular events after venous thromboembolism: a systematic review and a meta-analysis

Summary.u2002 Background: Whether patients with unprovoked venous thromboembolism (VTE) have a higher risk of arterial cardiovascular events than the general population and patients with provoked VTE is a matter of debate. Objective: To perform a systematic review and a meta‐analysis aimed at assessing the risk of arterial cardiovascular events in patients with unprovoked VTE as compared with both patients with provoked VTE and controls. Methods: A systematic search was performed. Studies reporting on (i) patients with confirmed VTE, (ii) a follow‐up of at least 6 months and (iii) the incidence of arterial cardiovascular events (acute myocardial infarction and ischemic stroke) were included in the systematic review. Those studies reporting separate incidences of cardiovascular events in patients with unprovoked and provoked VTE or patients with unprovoked VTE and controls were included in the incidence rate meta‐analysis. Results: Overall, 17 studies were included in the systematic review. The weighted mean incidence of arterial cardiovascular events was 0.46% [95% confidence interval (CI) 0.34–0.59] and 0.35% (95% CI 0.24–0.49) per patient‐year in patients with unprovoked and provoked VTE, respectively. Six studies were included in the meta‐analysis. The risk of arterial cardiovascular events appeared to be higher in patients with unprovoked VTE than in controls [incidence rate ratio (IRR) 1.87, 95% CI 1.32–2.65] and than in patients with provoked VTE (IRR 1.86, 95% CI 1.19–2.89). Conclusions: Patients with unprovoked VTE have a higher risk of arterial cardiovascular events than patients with provoked VTE over long‐term follow‐up.

Multidetector CT scan for acute pulmonary embolism: Embolic burden and clinical outcome

BACKGROUNDnIn patients with acute pulmonary embolism (PE), the correlation between the embolic burden assessed by multidetector CT (MDCT) scan and clinical outcomes remains unclear. Patients with symptomatic acute PE diagnosed based on MDCT angiography were included in a multicenter study aimed at assessing the prognostic role of the embolic burden evaluated with MDCT scan.nnnMETHODSnEmbolic burden was assessed as (1) localization of the emboli as central (saddle or at least one main pulmonary artery), lobar, or distal (segmental or subsegmental arteries) and (2) the obstruction index by the scoring system of Qanadli. The primary outcome was 30-day all-cause death or clinical deterioration. Predictors of all-cause death or clinical deterioration were identified by Cox regression statistics.nnnRESULTSnOverall, 579 patients were included in the study; 60 (10.4%) died or had clinical deterioration at 30 days. Central localization of emboli was not associated with all-cause death or clinical deterioration (hazard ratio [HR], 2.42; 95% CI, 0.77-7.59; P 5 .13). However, in 516 hemodynamically stable patients, central localization of emboli (HR, 8.3; 95% CI, 1.0-67; P 5 .047) was an independent predictor of all-cause death or clinical deterioration, whereas distal emboli were inversely associated with these outcome events (HR, 0.12; 95% CI, 0.015-0.97; P 5 .047). No correlation was found between obstruction index (evaluated in 448 patients) and all-cause death or clinical deterioration in the overall study population and in the hemodynamically stable patients.nnnCONCLUSIONSnIn hemodynamically stable patients with acute PE, central emboli are associated with an increased risk for all-cause death or clinical deterioration. This risk is low in patients with segmental or subsegmental PE.

A Randomized Study on 1-Week Versus 4-Week Prophylaxis for Venous Thromboembolism After Laparoscopic Surgery for Colorectal Cancer

Objective:To compare the efficacy and safety of antithrombotic prophylaxis given for 1 week or 4 weeks in patients undergoing laparoscopic surgery for colorectal cancer. Background:Extending antithrombotic prophylaxis beyond 1 week reduces the incidence of venous thromboembolism (VTE) after open abdominal surgery for cancer. Methods:In consecutive patients who underwent laparoscopic surgery for colorectal cancer, complete compression ultrasonography of the lower limbs was performed after 8 ± 2 days of antithrombotic prophylaxis. Patients with no evidence of VTE were randomized to short (heparin withdrawal) or to extended (heparin continued for 3 additional weeks) prophylaxis. Complete compression ultrasonography was repeated at day 28 ± 2 after surgery by investigators blinded to treatment allocation. The primary outcome of the study was the composite of symptomatic and ultrasonography-detected VTE at day 28 ± 2 after surgery. Results:Overall, 301 patients were evaluated for inclusion in the study and 225 were randomized. VTE occurred in 11 of 113 patients randomized to short (9.7%) and in none of the 112 patients randomized to extended heparin prophylaxis (P = 0.001). The incidence of VTE at 3 months was 9.7% and 0.9% in patients randomized to short or to extended heparin prophylaxis, respectively (relative risk reduction: 91%, 95% confidence interval: 30%–99%; P = 0.005). The rate of bleeding was similar in the 2 treatment groups. Two patients died during the study period, 1 in each treatment group. Conclusions:After laparoscopic surgery for colorectal cancer, extended antithrombotic prophylaxis is safe and reduces the risk for VTE as compared with 1-week prophylaxis (NCT01589146).

Prognostic role of embolic burden assessed at computed tomography angiography in patients with acute pulmonary embolism: systematic review and meta‐analysis

In patients with acute pulmonary embolism (PE), risk stratification is indicated for tailoring of both diagnostic strategies and acute treatment. Whether embolic burden assessed at computed tomography (CT) angiography has a role in risk stratification in these patients is debated.

Old and new oral anticoagulants for venous thromboembolism and atrial fibrillation: A review of the literature

Heparin, fondaparinux and vitamin K antagonists (VKAs) are effective for the prevention and treatment of venous thromboembolism. VKAs reduce by almost 60% the rate of cardioembolic complications in patients with atrial fibrillation. The risk for bleeding and the inconvenience for laboratory monitoring, dose adjustment and drug or food interactions are the main limits for VKAs while parenteral administration is the main limit for heparin and fondaparinux. New oral anticoagulants with more predictable anticoagulant response and no need for laboratory monitoring have been shown to be effective for the prevention and treatment of venous thromboembolism and for the prevention of stroke and systemic embolism in patients with atrial fibrillation. The pharmacokinetic and pharmacodynamic profile of the new agents differ for mechanisms of action - mainly anti Xa and one antithrombin agent- bioavailability, half life, renal or live clearance. Drug interactions have been described with the new agents and inhibitors or inducers of P-gp or CYP3A4. Overall, in the prevention of venous thromboembolism after major elective orthopaedic surgery dabigatran was shown to be non-inferior, rivaroxaban and apixaban to be superior to enoxaparin. Both, rivaroxaban and dabigatran were shown to be non-inferior to low-molecular weight heparin and VKAs for the treatment of venous thromboembolism. Dabigatran 150mg twice daily reduced the incidence of both ischemic and hemorrhagic stroke in patients with atrial fibrillation respect to warfarin. In these patients rivaroxaban and apixaban reduced the incidence of hemorrhagic stroke with a similar incidence of ischemic stroke. No bleeding concern emerged with the new anticoagulant agents in this indication.

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

INTRODUCTIONnPrimary 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.nnnMATERIALS AND METHODSnPatients 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.nnnRESULTSnTwenty 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.nnnCONCLUSIONSnEndothelial 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.