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Concept: Pulmonary embolism


Background The prevalence of pulmonary embolism among patients hospitalized for syncope is not well documented, and current guidelines pay little attention to a diagnostic workup for pulmonary embolism in these patients. Methods We performed a systematic workup for pulmonary embolism in patients admitted to 11 hospitals in Italy for a first episode of syncope, regardless of whether there were alternative explanations for the syncope. The diagnosis of pulmonary embolism was ruled out in patients who had a low pretest clinical probability, which was defined according to the Wells score, in combination with a negative d-dimer assay. In all other patients, computed tomographic pulmonary angiography or ventilation-perfusion lung scanning was performed. Results A total of 560 patients (mean age, 76 years) were included in the study. A diagnosis of pulmonary embolism was ruled out in 330 of the 560 patients (58.9%) on the basis of the combination of a low pretest clinical probability of pulmonary embolism and negative d-dimer assay. Among the remaining 230 patients, pulmonary embolism was identified in 97 (42.2%). In the entire cohort, the prevalence of pulmonary embolism was 17.3% (95% confidence interval, 14.2 to 20.5). Evidence of an embolus in a main pulmonary or lobar artery or evidence of perfusion defects larger than 25% of the total area of both lungs was found in 61 patients. Pulmonary embolism was identified in 45 of the 355 patients (12.7%) who had an alternative explanation for syncope and in 52 of the 205 patients (25.4%) who did not. Conclusions Pulmonary embolism was identified in nearly one of every six patients hospitalized for a first episode of syncope. (Funded by the University of Padua; PESIT number, NCT01797289 .).

Concepts: Clinical trial, Lung, Hospital, Heart, Pulmonary embolism, Pulmonary artery, Human lung, Embolism


Background In patients with ischemic stroke, endovascular treatment results in a higher rate of recanalization of the affected cerebral artery than systemic intravenous thrombolytic therapy. However, comparison of the clinical efficacy of the two approaches is needed. Methods We randomly assigned 362 patients with acute ischemic stroke, within 4.5 hours after onset, to endovascular therapy (intraarterial thrombolysis with recombinant tissue plasminogen activator [t-PA], mechanical clot disruption or retrieval, or a combination of these approaches) or intravenous t-PA. Treatments were to be given as soon as possible after randomization. The primary outcome was survival free of disability (defined as a modified Rankin score of 0 or 1 on a scale of 0 to 6, with 0 indicating no symptoms, 1 no clinically significant disability despite symptoms, and 6 death) at 3 months. Results A total of 181 patients were assigned to receive endovascular therapy, and 181 intravenous t-PA. The median time from stroke onset to the start of treatment was 3.75 hours for endovascular therapy and 2.75 hours for intravenous t-PA (P<0.001). At 3 months, 55 patients in the endovascular-therapy group (30.4%) and 63 in the intravenous t-PA group (34.8%) were alive without disability (odds ratio adjusted for age, sex, stroke severity, and atrial fibrillation status at baseline, 0.71; 95% confidence interval, 0.44 to 1.14; P=0.16). Fatal or nonfatal symptomatic intracranial hemorrhage within 7 days occurred in 6% of the patients in each group, and there were no significant differences between groups in the rates of other serious adverse events or the case fatality rate. Conclusions The results of this trial in patients with acute ischemic stroke indicate that endovascular therapy is not superior to standard treatment with intravenous t-PA. (Funded by the Italian Medicines Agency, number, NCT00640367 .).

Concepts: Clinical trial, Myocardial infarction, Stroke, Atrial fibrillation, Pulmonary embolism, Tissue plasminogen activator, Thrombolysis, Plasmin


Background It is uncertain whether bridging anticoagulation is necessary for patients with atrial fibrillation who need an interruption in warfarin treatment for an elective operation or other elective invasive procedure. We hypothesized that forgoing bridging anticoagulation would be noninferior to bridging with low-molecular-weight heparin for the prevention of perioperative arterial thromboembolism and would be superior to bridging with respect to major bleeding. Methods We performed a randomized, double-blind, placebo-controlled trial in which, after perioperative interruption of warfarin therapy, patients were randomly assigned to receive bridging anticoagulation therapy with low-molecular-weight heparin (100 IU of dalteparin per kilogram of body weight) or matching placebo administered subcutaneously twice daily, from 3 days before the procedure until 24 hours before the procedure and then for 5 to 10 days after the procedure. Warfarin treatment was stopped 5 days before the procedure and was resumed within 24 hours after the procedure. Follow-up of patients continued for 30 days after the procedure. The primary outcomes were arterial thromboembolism (stroke, systemic embolism, or transient ischemic attack) and major bleeding. Results In total, 1884 patients were enrolled, with 950 assigned to receive no bridging therapy and 934 assigned to receive bridging therapy. The incidence of arterial thromboembolism was 0.4% in the no-bridging group and 0.3% in the bridging group (risk difference, 0.1 percentage points; 95% confidence interval [CI], -0.6 to 0.8; P=0.01 for noninferiority). The incidence of major bleeding was 1.3% in the no-bridging group and 3.2% in the bridging group (relative risk, 0.41; 95% CI, 0.20 to 0.78; P=0.005 for superiority). Conclusions In patients with atrial fibrillation who had warfarin treatment interrupted for an elective operation or other elective invasive procedure, forgoing bridging anticoagulation was noninferior to perioperative bridging with low-molecular-weight heparin for the prevention of arterial thromboembolism and decreased the risk of major bleeding. (Funded by the National Heart, Lung, and Blood Institute of the National Institutes of Health; BRIDGE number, NCT00786474 .).

Concepts: Blood, Stroke, Atrial fibrillation, Thrombosis, Pulmonary embolism, Warfarin, Anticoagulant, Heparin


Effective treatment of venous thromboembolism (VTE) strikes a balance between prevention of recurrence and bleeding complications. The current standard of care is heparin followed by a vitamin K antagonist such as warfarin. However, this option is not without its limitations, as the anticoagulant effect of warfarin is associated with high inter- and intra-patient variability and patients must be regularly monitored to ensure that anticoagulation is within the narrow target therapeutic range. Several novel oral anticoagulant agents are in the advanced stages of development for VTE treatment, some of which are given after an initial period of heparin treatment, in line with current practice, while others switch from high to low doses after the initial phase of treatment. In this review we assess the critical considerations for treating VTE in light of emerging clinical data for new oral agents and discuss the merits of novel treatment regimens for patients who have experienced an episode of deep vein thrombosis or pulmonary embolism.

Concepts: Stroke, Thrombosis, Pulmonary embolism, Warfarin, Vein, Low molecular weight heparin, Anticoagulant, Deep vein thrombosis


Paradoxical embolism (PDE) occurs after embolic material passes from the venous to the arterial circulation through a right-to-left shunt, which is frequently a patent foramen ovale (PFO). We describe the case of a patient with deep venous thrombosis and an intracardiac thrombus straddling a PFO and who was successfully treated with an emergency surgery.

Concepts: Blood vessel, Stroke, Pulmonary embolism, Hematology, Vein, Atrial septal defect, Foramen ovale, Embolism


Background The use of thromboprophylaxis to prevent clinically apparent venous thromboembolism after knee arthroscopy or casting of the lower leg is disputed. We compared the incidence of symptomatic venous thromboembolism after these procedures between patients who received anticoagulant therapy and those who received no anticoagulant therapy. Methods We conducted two parallel, pragmatic, multicenter, randomized, controlled, open-label trials with blinded outcome evaluation: the POT-KAST trial, which included patients undergoing knee arthroscopy, and the POT-CAST trial, which included patients treated with casting of the lower leg. Patients were assigned to receive either a prophylactic dose of low-molecular-weight heparin (for the 8 days after arthroscopy in the POT-KAST trial or during the full period of immobilization due to casting in the POT-CAST trial) or no anticoagulant therapy. The primary outcomes were the cumulative incidences of symptomatic venous thromboembolism and major bleeding within 3 months after the procedure. Results In the POT-KAST trial, 1543 patients underwent randomization, of whom 1451 were included in the intention-to-treat population. Venous thromboembolism occurred in 5 of the 731 patients (0.7%) in the treatment group and in 3 of the 720 patients (0.4%) in the control group (relative risk, 1.6; 95% confidence interval [CI], 0.4 to 6.8; absolute difference in risk, 0.3 percentage points; 95% CI, -0.6 to 1.2). Major bleeding occurred in 1 patient (0.1%) in the treatment group and in 1 (0.1%) in the control group (absolute difference in risk, 0 percentage points; 95% CI, -0.6 to 0.7). In the POT-CAST trial, 1519 patients underwent randomization, of whom 1435 were included in the intention-to-treat population. Venous thromboembolism occurred in 10 of the 719 patients (1.4%) in the treatment group and in 13 of the 716 patients (1.8%) in the control group (relative risk, 0.8; 95% CI, 0.3 to 1.7; absolute difference in risk, -0.4 percentage points; 95% CI, -1.8 to 1.0). No major bleeding events occurred. In both trials, the most common adverse event was infection. Conclusions The results of our trials showed that prophylaxis with low-molecular-weight heparin for the 8 days after knee arthroscopy or during the full period of immobilization due to casting was not effective for the prevention of symptomatic venous thromboembolism. (Funded by the Netherlands Organization for Health Research and Development; POT-KAST and POT-CAST numbers, NCT01542723 and NCT01542762 , respectively.).

Concepts: Blood, Thrombosis, Pulmonary embolism, Warfarin, Anterior cruciate ligament, Low molecular weight heparin, Anticoagulant, Heparin


IMPORTANCE Retrievable inferior vena cava (IVC) filters were designed to provide temporary protection from pulmonary embolism, sparing patients from long-term complications of permanent filters. However, many retrievable IVC filters are left in place indefinitely. OBJECTIVES To review the medical records of patients with IVC filters to determine patient demographics and date of and indication for IVC filter placement, as well as complications, follow-up data, date of IVC filter retrieval, and use of anticoagulant therapy. DESIGN AND SETTING A retrospective review of IVC filter use between August 1, 2003, and February 28, 2011, was conducted at Boston Medical Center, a tertiary referral center with the largest trauma center in New England. PARTICIPANTS In total, 978 patients. Twenty six patients were excluded from the study because of incomplete medical records. INTERVENTION Placement of retrievable IVC filter. MAIN OUTCOME MEASURES In total, 952 medical records were included in the analysis. RESULTS Of 679 retrievable IVC filters that were placed, 58 (8.5%) were successfully removed. Unsuccessful retrieval attempts were made in 13 patients (18.3% of attempts). Seventy-four venous thrombotic events (7.8% of 952 patients included in the study) occurred after IVC filter placement, including 25 pulmonary emboli, all of which occurred with the IVC filter in place. Forty-eight percent of venous thrombotic events were in patients without venous thromboembolism at the time of IVC filter placement, and 89.4% occurred in patients not receiving anticoagulants. Many IVC filters placed after trauma were inserted when the highest bleeding risk had subsided, and anticoagulant therapy may have been appropriate. While many of these filters were placed because of a perceived contraindication to anticoagulants, 237 patients (24.9%) were discharged on a regimen of anticoagulant therapy. CONCLUSION AND RELEVANCE Our research suggests that the use of IVC filters for prophylaxis and treatment of venous thrombotic events, combined with a low retrieval rate and inconsistent use of anticoagulant therapy, results in suboptimal outcomes due to high rates of venous thromboembolism.

Concepts: Stroke, Pulmonary embolism, Warfarin, Low molecular weight heparin, Anticoagulant, Inferior vena cava, Deep vein thrombosis, Inferior vena cava filter


To determine the real world risk of gastrointestinal bleeding associated with the use of the novel oral anticoagulants dabigatran and rivaroxaban compared with warfarin.

Concepts: Atrial fibrillation, Thrombosis, Pulmonary embolism, Warfarin, Anticoagulant, Heparin, Dabigatran, Anticoagulants


Marlise Muñoz was 33 years old and the mother of a 15-month-old when she collapsed on November 26, 2013, from what was later determined to be a massive pulmonary embolism. Initially described as apneic but alive, she was brought to the county hospital where her family was soon told that she was brain dead. Ms. Muñoz and her husband, both emergency medical technicians (EMTs), had discussed their feelings about such situations. So Erik Muñoz felt confident in asserting that his wife would not want continued support. Her other family members agreed, and they requested withdrawal of ventilation and other measures . . .

Concepts: Family, Marriage, Shock, Pulmonary embolism, Mother, Emergency medical services, Emergency medical technician, Wife


Treatment guidelines for acute pulmonary embolism (PE) recommend risk stratifying patients to assess PE severity, as those at higher risk should be considered for therapy in addition to standard anticoagulation to prevent right ventricular (RV) failure, which can cause hemodynamic collapse. The hypothesis was that 12-lead electrocardiography (ECG) can aid in this determination. The objective of this study was to measure the prognostic value of specific ECG findings (the Daniel score, which includes heart rate > 100 beats/min, presence of the S1Q3T3 pattern, incomplete and complete right bundle branch block [RBBB], and T-wave inversion in leads V1-V4, plus ST elevation in lead aVR and atrial fibrillation suggestive of RV strain from acute pulmonary hypertension), in patients with acute PE.

Concepts: Cardiology, Heart, Atrial fibrillation, Pulmonary embolism, Cardiac electrophysiology, Thrombus, Pulmonary artery, Ventricular fibrillation