Catheter-directed ultrasound-accelerated thrombolysis for the treatment of acute pulmonary embolism

Systemic thrombolysis rapidly improves right ventricular (RV) dysfunction in patients with acute pulmonary embolism (PE) but is associated with major bleeding complications in up to 20%. The efficacy of low-dose, catheter-directed ultrasound-accelerated thrombolysis (USAT) on the reversal of RV dysfunction is unknown.

Randomized clinical trial comparing percutaneous closure of patent foramen ovale (PFO) using the Amplatzer PFO Occluder with medical treatment in patients with cryptogenic embolism (PC-Trial): rationale and design

Background Several studies have shown an association of cryptogenic stroke and embolism with patent foramen ovale (PFO), but the question how to prevent further events in such patients is unresolved. Options include antithrombotic treatment with warfarin or antiplatelet agents or surgical or endovascular closure of the PFO. The PC-Trial was set up to compare endovascular closure and best medical treatment for prevention of recurrent events. Methods The PC-Trial is a randomized clinical trial comparing the efficacy of percutaneous closure of the PFO using the Amplatzer PFO occluder with best medical treatment in patients with cryptogenic embolism, i.e. mostly cryptogenic stroke. Warfarin for 6 months followed by antiplatelet agents is recommended as medical treatment. Randomization is stratified according to patients age (<45 versus ≥45 years), presence of atrial septal aneurysm (ASA yes or no) and number of embolic events before randomization (one versus more than one event). Primary endpoints are death, nonfatal stroke and peripheral embolism. Discussion patients were randomized in 29 centers of Europe, Canada, and Australia. Randomization started February 2000. Enrollment of 414 patients was completed in February 2009. All patients will be followed-up longitudinally. Follow-up is maintained until the last enrolled patient is beyond 2.5 years of follow-up (expected in 2011).

Fatal pulmonary embolism in a premature neonate after twin-to-twin transfusion syndrome

Thrombotic events are being increasingly recognized during the neonatal period. An infant girl was born at 29 weeks' gestation after a pregnancy complicated by twin-to-twin transfusion syndrome. After an initial uncomplicated clinical course, her oxygen requirement increased, which was interpreted as an early sign of bronchopulmonary dysplasia. At 3 weeks of age, she suddenly collapsed and died of severe pulmonary hypertension. At autopsy, multiple pulmonary artery emboli and several older renal vein thromboses were found. Results of genetic analyses of the infant and her family were negative for thrombophilia. Although embolism represents a frequent emergency in adults, fatal pulmonary embolism has never, to our knowledge, been described for premature infants. This case suggests that thrombotic events are underdiagnosed and that additional studies are needed to define infants at risk and optimal treatment strategies.

Predictors of in-hospital mortality in elderly patients with acute venous thrombo-embolism: the SWIss Venous ThromboEmbolism Registry (SWIVTER)

Although acute venous thrombo-embolism (VTE) often afflicts patients with advanced age, the predictors of in-hospital mortality for elderly VTE patients are unknown.

Cardiac troponin testing and the simplified Pulmonary Embolism Severity Index. The SWIss Venous ThromboEmbolism Registry (SWIVTER)

A low simplified Pulmonary Embolism Severity Index (sPESI), defined as age ≤80 years and absence of systemic hypotension, tachycardia, hypoxia, cancer, heart failure, and lung disease, identifies low-risk patients with acute pulmonary embolism (PE). It is unknown whether cardiac troponin testing improves the prediction of clinical outcomes if the sPESI is not low. In the prospective Swiss Venous Thromboembolism Registry, 369 patients with acute PE and a troponin test (conventional troponin T or I, highly sensitive troponin T) were enrolled from 18 hospitals. A positive test result was defined as a troponin level above the manufacturers assay threshold. Among the 106 (29%) patients with low sPESI, the rate of mortality or PE recurrence at 30 days was 1.0%. Among the 263 (71%) patients with high sPESI, 177 (67%) were troponin-negative and 86 (33%) troponin-positive; the rate of mortality or PE recurrence at 30 days was 4.6% vs. 12.8% (p=0.015), respectively. Overall, risk assessment with a troponin test (hazard ratio [HR] 3.39, 95% confidence interval [CI] 1.38-8.37; p=0.008) maintained its prognostic value for mortality or PE recurrence when adjusted for sPESI (HR 5.80, 95%CI 0.76-44.10; p=0.09). The combination of sPESI with a troponin test resulted in a greater area under the receiver-operating characteristic curve (HR 0.72, 95% CI 0.63-0.81) than sPESI alone (HR 0.63, 95% CI 0.57-0.68) (p=0.023). In conclusion, although cardiac troponin testing may not be required in patients with a low sPESI, it adds prognostic value for early death and recurrence for patients with a high sPESI.

Massive Systemic Fat Embolism Detected by Postmortem Imaging and Biopsy

Postmortem computed tomography (pmCT) and pmCT angiography (pmCTA) provide a minimally invasive method to determine the cause of death. Postmortem image-guided biopsy allows for precise sampling of histological specimens. This case study describes the findings of lethal systemic fat embolism (FE) on whole-body unenhanced pmCT, pmCTA, and image-guided biopsy, with autopsy and histopathologic correlation. Unenhanced pmCT revealed a distinct fat level on top of sedimented layers of corpuscular blood particles and serum in the arterial system and pulmonary trunk. Subsequent pmCTA showed reproducible results, and image-guided biopsy confirmed fatal FE. pm CT/pmCTA combined with image-guided biopsy established the cause of death as right heart failure as a result of systemic fatal FE prior to autopsy. All imaging findings were consistent with traditional autopsy and histological specimens. This unique case demonstrates new imaging findings in massive, fatal FE and highlights that postmortem imaging, supplemented by image-guided biopsy, may detect the cause of death prior to traditional autopsy.

A Minimally Invasive Technique for the Detection and Analysis of Pulmonary Fat Embolism: A Feasibility Study*

We investigated the feasibility of postmortem percutaneous needle biopsy (PNB) for obtaining pulmonary samples adequate for the study of pulmonary fat embolism (PFE). Samples of both lungs were obtained from 26 cadavers via two different methods: (i) PNB and (ii) the double-edged knife technique, the gold standard at our institute. After water storage and Sudan III staining, six forensic pathologists independently examined all samples for the presence and severity of PFE. The results were compared and analyzed in each case regarding the vitality of the PFE and its relationship to the cause of death. The results showed that PFE was almost identically diagnosed and graded on the samples obtained via both methods. The discrepancies between the two techniques did not affect the diagnoses of vitality or cause of death related to PFE. This study demonstrates the feasibility of the PNB sampling method for the diagnosis and interpretation of PFE in the postmortem setting.

Correlation of fat embolism severity and subcutaneous fatty tissue crushing and bone fractures

Pulmonary fat embolism (PFE) is frequently encountered in blunt trauma. The clinical manifestation ranges from no impairment in light cases to death due to right-sided heart failure or hypoxaemia in severe cases. Occasionally, pulmonary fat embolism can give rise to a fat embolism syndrome (FES), which is marked by multiorgan failure, respiratory disorders, petechiae and often death. It is well known that fractures of long bones can lead to PFE. Several authors have argued that PFE can arise due to mere soft tissue injury in the absence of fractures, a claim other authors disagree upon. In this study, we retrospectively examined 50 victims of blunt trauma with regard to grade and extent of fractures and crushing of subcutaneous fatty tissue and presence and severity of PFE. Our results indicate that PFE can arise due to mere crushing of subcutaneous fat and that the fracture grade correlated well with PFE severity (p = 0.011). The correlation between PFE and the fracture severity (body regions affected by fractures and fracture grade) showed a lesser significant correlation (p = 0.170). The survival time (p = 0.567), the amount of body regions affected by fat crushing (p = 0.336) and the fat crush grade (p = 0.485) did not correlate with the PFE grade, nor did the amount of body regions affected by fractures. These results may have clinical implications for the assessment of a possible FES development, as, if the risk of a PFE is known, preventive steps can be taken.

Outpatient versus inpatient treatment for patients with acute pulmonary embolism: an international, open-label, randomised, non-inferiority trial

Although practice guidelines recommend outpatient care for selected, haemodynamically stable patients with pulmonary embolism, most treatment is presently inpatient based. We aimed to assess non-inferiority of outpatient care compared with inpatient care.

A comparison of the original and simplified Pulmonary Embolism Severity Index

The Pulmonary Embolism Severity Index (PESI) is a validated clinical prognostic model for patients with pulmonary embolism (PE). Recently, a simplified version of the PESI was developed. We sought to compare the prognostic performance of the original and simplified PESI. Using data from 15,531 patients with PE, we compared the proportions of patients classified as low versus higher risk between the original and simplified PESI and estimated 30-day mortality within each risk group. To assess the models' accuracy to predict mortality, we calculated sensitivity, specificity, and predictive values and likelihood ratios for low- versus higher-risk patients. We also compared the models' discriminative power by calculating the area under the receiver-operating characteristic curve. The overall 30-day mortality was 9.3%. The original PESI classified a significantly greater proportion of patients as low-risk than the simplified PESI (40.9% vs. 36.8%; p<0.001). Low-risk patients based on the original and simplified PESI had a mortality of 2.3% and 2.7%, respectively. The original and simplified PESI had similar sensitivities (90% vs. 89%), negative predictive values (98% vs. 97%), and negative likelihood ratios (0.23 vs. 0.28) for predicting mortality. The original PESI had a significantly greater discriminatory power than the simplified PESI (area under the ROC curve 0.78 [95% CI: 0.77-0.79] vs. 0.72 [95% CI: 0.71-0.74]; p<0.001). In conclusion, even though the simplified PESI accurately identified patients at low-risk of adverse outcomes, the original PESI classified a higher proportion of patients as low-risk and had a greater discriminatory power than the simplified PESI.

The effects of cause of death classification on prognostic assessment of patients with pulmonary embolism

Although previous studies have provided evidence that the majority of deaths following an acute pulmonary embolism (PE) directly relate to the PE, more recent registries and cohort studies suggest otherwise.

A strategy combining imaging and laboratory biomarkers in comparison with a simplified clinical score for risk stratification of patients with acute pulmonary embolism

This study aimed to assess the performance of two prognostic models-the European Society of Cardiology (ESC) model and the simplified Pulmonary Embolism Severity Index (sPESI)-in predicting short-term mortality in patients with pulmonary embolism (PE).