Pulmonary Embolism Severity Research Articles

Amplified Thrombo-Inflammatory Biomarkers in Pulmonary Embolism with Augmented Responses in Von-Willebrand Factor, Microparticles and Interleukin-6 in Patients with Cancer

Introduction: The multifactorial and complex pathophysiology of pulmonary embolism (PE) involves dysregulation of hemostatic system including fibrinolytic imbalance, endothelial compromise, and generation of thrombotic mediators, along with cellular defects and hemodynamic derangement. These pathophysiologic processes results in the generation of thrombo-inflammatory biomarkers reflecting the endogenous hemostatic imbalance. Cancer is prevalent in PE patients and is considered as an added risk factor for the adverse outcomes. Thrombo-inflammatory biomarker profiling provide means to risk stratify PE patients. This study aimed to profile several of these biomarkers in normal individuals and PE patients and further demonstrate their additional amplification in patients with cancer as a co-morbidity. Materials & Method: Four hundred male and female patients of 18 years or older age, were included through enrolment in conjunction with an IRB approved project by the pulmonary embolism response team (PERT) registry. Diagnosis of PE was confirmed by computed tomography (CT), angiography or ventilation perfusion imaging. Blood samples were drawn with in 24-72 hours of confirmed diagnosis of acute PE. Normal human plasma (NHP) samples were obtained from 50 healthy individuals including 25 male and 25 female and used for referencing purposes. All of the plasma samples were analyzed for D-Dimer, plasminogen activator inhibitor-1 (PAI-1) antigen, tissue-type plasminogen activator (tPA), activated thrombin-activatable fibrinolysis inhibitor (TAFI-a), von Willebrand factor (vWF), c-Reactive Protein (CRP) and interleukin-6 (IL-6) were measured by commercially available ELISA methods. Microparticles were measured by using a chromogenic functional method. Individual biomarkers were compared to normal plasma and further stratified on cancer status and PE severity. Results are presented as mean±SD and fold increase. For the degree of association, GraphPad Prism Software was used. Results: PE patients exhibited varying levels of upregulation of all of the individual biomarkers compared to normal's, D-Dimer (37.05-fold), PAI-1 antigen (3.95-fold), tPA (4.69-fold), TAFI (1.21-fold), vWF (1.89-fold), CRP (35.34-fold), IL-6 (21.62-fold), and microparticles (3.04-fold) increase in PE patients with reference to NHP. When the PE group stratified into cancer and non-cancer patients, most of the biomarkers except D-Dimer and microparticles showed varying degree of modest elevation in the cancer group (figure 1). vWF, IL6 and microparticles levels were found to be further amplified in PE group with cancer. Of these three biomarkers, only vWF remained amplified when stratified by PE severity in patients with cancer, however this change was only observed in the low-grade PE patients (table 1). The IL-6 levels showed increased trend in the low-grade and sub-massive patient group, however because of the wide scatter, it was not significant. Conclusion: These studies demonstrate that thrombo-inflammatory biomarkers are upregulated in PE patients. Furthermore, PE patients with cancer exhibit amplified responses for vWF, IL-6 and microparticles levels suggesting their role in mediating the pathogenesis involving endothelial, inflammatory and thrombogenic mechanisms. Among the biomarkers studied, vWF is central to thrombo-inflammatory process and is distinct in PE cohort with cancer, despite taking into account the lower PE severity. These studies suggest that selective biomarker profiling of thrombo-inflammatory biomarkers may be valuable in the risk stratification and therapeutic management of PE patients at large. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Endogenous Thrombin Generation Potential in Patients with Pulmonary Embolism and Its Relevance to Thrombo-Inflammatory Biomarkers

Background: Pulmonary embolism (PE) is a catastrophic outcome in patients with venous thrombosis and third leading cardiovascular cause of death after myocardial infraction and stroke, estimates around 100,000 deaths annually.Inflammation, hemostatic dysregulation including fibrinolytic imbalance, endothelial compromise, and generation of thrombotic mediators, along with cellular defects and hemodynamic derangement contribute to the pathogenesis of PE.Endogenous thrombin generation contributes to the overall pathology of PE. The purpose of this study is to investigate endogenous thrombin potential (ETP) and the circulating biomarkers of fibrinolytic, inflammatory, and endothelial dysfunction in PE samples. Methods: Citrated blood samples from 400 patients with confirmed PE were collected at Loyola University Medical Center and Gottlieb Memorial Hospital under an IRB approved protocol. Normal human plasma (NHP) comprised of 25 male and 25 female samples were obtained from a commercial source. Thrombin generation studies were carried out using a commercially available a kinetic system. Endogenous GAG's contents were measured by fluorogenic quenching method. Thrombin generation parameters such as peak thrombin, lag time and area under the curve (AUC) were compiled. Plasma samples were retrospectively analyzed for biomarkers, including D-Dimer, PAI-1, tPA, TAFIa, vWF, CRP, IL6, TFPI and VEGF using commercially available sandwich ELISA methods. Results were compiled as mean ± SD and analyzed for significance and correlation by using GraphPad Prism software. Result: On a cumulative basis, PE patients showed a wide variation in thrombin generation parameters (Table 1). Biomarker analysis showed elevated levels of D-Dimer (37.05-fold), CRP (35.34-folds), IL6 (21.62-folds), tPA (4.69-folds), PAI-1a (3.95-folds), VEGF (2.38-folds), TFPI (2.17-folds), GAG's (1.92-folds), vWF (1.89-folds), and TAFIa (1.21-folds). Peak thrombin levels exhibited varying degree of positive and negative correlations with various biomarkers as illustrated in figure 1. Thrombin levels showed significant negative correlations with tPA, endogenous GAG's & TFPI, while positively correlated with VEGF. D-dimer showed positive correlations with CRP & IL6. PAI-1 demonstrated positive correlations with tPA, IL6, and endogenous GAG's. tPA showed negative correlation with TAFI, while positive correlations with endogenous GAG's, and TFPI. vWF showed positive correlations CRP, IL6, and endogenous GAG's. CRP showed positive correlations with IL6. Endogenous GAG's showed positive correlations with TFPI while TFPI showed negative correlation with VEGF. Conclusion: PE patients exhibit a wide variation in endogenous thrombin generation parameters. Overall, peak thrombin and ETP were decreased, whereas the lag time was increased. The increase in thrombo-inflammatory markers is suggestive of upregulation of thrombogenesis, and inflammatory processes in these patients. Thus, the profiling of thrombo-inflammatory biomarkers along with thrombin generation profile may provide additional information on the pathogenesis and severity of PE. However, biomarkers of hemostatic activation, vascular dysfunction and inflammation were increased. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Elevated Thrombin Generation Biomarkers and Their Relevance with Decreased Thrombin Generation Potential in Patients with Pulmonary Embolism

Background: Pulmonary embolism (PE) is a catastrophic complication in patients with venous thrombosis and is the third leading cardiovascular cause of death after myocardial infraction and stroke. Inflammation, hemostatic dysregulation, and generation of thrombotic mediators contribute to the pathogenesis of PE. Persistent thrombin generation contributes to the overall pathology of PE. The purpose of this study is to investigate endogenous thrombin potential (ETP) in PE patients and demonstrate its relationship with thrombin generation biomarkers, such as prothrombin fragment 1+2 (F1+2), thrombin anti-thrombin complex (TAT) and D-Dimer. Methods: Citrated blood samples from 201 patients with confirmed PE were collected under an IRB approved protocol. Fifty normal human plasma (NHP) samples were used as a reference. Thrombin generation studies were carried out by using fluorogenic substrate method (calibrated automated thrombogram, Diagnostica Stago; Paris, France). Thrombin generation parameters such as peak thrombin, lag time and endogenous thrombin potential (ETP) were compiled. Plasma samples were analyzed for such biomarkers as prothrombin fragment 1+2 (F1+2), thrombin anti-thrombin complex (TAT), and D-Dimer by using commercially available Sandwich ELISA methods. Results were compiled as mean ± SD and applicable statistical analysis was performed by using GraphPad Prism software. Result: PE patients exhibited a wide variation in thrombin generation parameters. ETP in PE patients decreased to 549.2±508.4 nM*min compared to NHP 701.8±214.6 nM*min, thrombin levels in PE patients also decreased to 83.7±80.1 nM compared to NHP 158.5±31.5 nM, while lag time increased 5.4±12.7 mins to 2.6±0.6 mins compared to NHP. Biomarker analysis showed elevated levels of F1+2 (972.3±1508.0 vs 294.2±105.0 pmol/L, 3.3-fold), TAT (34.9±54.3 vs 2.3±1.1ug/L, 15.3-fold), and D-Dimer (6720.0±4810.0 vs 182.6±205.8 ug/ml, 36.8-fold) compared to NHP. Endogenous thrombin potential levels demonstrate moderate and positive correlations with F1+2 (r = 0.22) while weak correlations were noted with TAT (r = 0.14) and D-Dimer (r = 0.05). F1+2 possess strong correlation with TAT (r = 0.55) and moderate for D-Dimer (r = 0.21). TAT also showed strong correlation with D-Dimer (r = 0.45). Thrombin generation parameters and biomarker levels based on PE severity has been shown in figure 1. Marked increase in thrombin generation biomarker levels were noted with increase PE severity. However, for the thrombin generation parameters, there is no differences were noted between the low grade and sub-massive PE, while the ETP and peak thrombin levels decreased, and lag time increased for the massive PE. Conclusion: These studies suggest that persistent thrombin generation in PE patients results in the consumption of prothrombin complex. However, such biomarkers of thrombin generation as F1+2, TAT and D-Dimer are formed, leading to higher circulating levels. Simultaneous measurement of thrombin generation biomarkers and thrombin generation parameters may be useful to determine the pathogenesis of thrombotic complications and optimization of treatment options. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Abstract 14219: Are There Sex Differences in the Imaging Modalities and Early Use of Echocardiography in Elderly Patients With Pulmonary Embolism?

Background: Sex differences in symptoms of acute pulmonary embolism (PE) in older adults (aged ≥65 years) may correlate with differences in the imaging modality used for confirming PE. It is also unknown if sex disparities exist in early use of echocardiography for prognostication. Methods: Using data from RIETE, a prospective multinational registry of patients with venous thromboembolism, we included older adults with acute PE. We compared the diagnostic modalities that were used in women vs men to confirm PE. We assessed the presenting symptoms/signs, thrombus location in patients diagnosed with computed tomography pulmonary angiography (CTPA), and evaluated PE severity according to the simplified Pulmonary Embolism Severity Index (sPESI) and the European Society of Cardiology (ESC) categories. We investigated the use of echocardiography within 3 days of PE diagnosis by sex. Results: REITE had 33,462 PE patients ≥65 years old including 19,294 women (mean age: 78.6±7.4 years) and 14,168 men (mean age: 76.1±7.2 years). CTPA was the dominant modality for PE diagnosis in both sexes, although a slightly smaller proportion of women were diagnosed with CTPA (77.1 vs 79.4, P<0.001). There were no sex differences in the proportion of patients presenting with isolated subsegmental PE (5.0%; 99% CI, 4.6-5.5% vs 5.5% 99% CI, 5.0-6.0%). There were no clinically relevant sex differences according to sPESI or the ESC risk categories (Table). Women were not less likely, indeed slightly more likely, than men to undergo echocardiography within 3 days of PE diagnosis (51.1%; 99% CI, 50.3-51.9% vs 48.9%; 99% CI, 48.0-49.8%). Conclusions: Slightly greater use of CTPA for diagnosing PE in men compared to women may reflect more chest pain and hemoptysis on presentation in men. However, there is similar illness severity in elderly men and women and minimal disparity in early use of echocardiography after diagnosis for prognostication.

Abstract 12497: Pulmonary Embolism Mortality Prediction With Deep Learning Based on Computed Tomographic Pulmonary Angiography and Clinical Data

Introduction: Pulmonary embolism (PE) is a significant cause of mortality in the United States. We aimed to develop deep learning models using computed tomographic pulmonary angiography (CTPA) and clinical data to predict mortality in patients with PE. Hypothesis: Deep learning models based on CTPA and clinical data will outperform PE Severity Index (PESI) in predicting PE mortality. Methods: A total of 927 patients (163 deceased, median age 64, range 13-99, 52% female) and 3978 total CTPAs were identified via retrospective review across three institutions. Data from one institution were randomly split 7:1:2 into training, validation, and internal testing sets. Data from the two remaining institutions were used as an external testing set. Imaging features extracted from PEnet and clinical data (PESI variables) were used to train Random Survival Forest models. Performance was evaluated with concordance index (c-index) and compared to PESI predictions with the Wilcoxon signed-rank test. Kaplan-Meier analysis was performed by stratifying patients into high- and low-risk groups based on the combined imaging and clinical model prediction. Results: Models based on (a) imaging, (b) clinical, and (c) combined imaging and clinical data achieved c-index values of 0.761, 0.774, and 0.843, respectively, on the internal testing set, and 0.660, 0.713, and 0.722 on the external testing set. For both data sets, the combined model outperformed PESI (0.740 and 0.709, respectively, both p<0.001). When stratifying patients into high- and low-risk groups, mortality outcomes were significantly different (p<0.001, Figure). Conclusions: Deep learning models based on combined CTPA features and clinical data outperform PESI for mortality prediction in PE. The addition of imaging to clinical features improves performance compared to clinical features alone.

PULMONARY EMBOLISM RISK STRATIFICATION IN PATIENTS WITH COVID-19 AND ACUTE PULMONARY EMBOLISM

PULMONARY EMBOLISM RISK STRATIFICATION IN PATIENTS WITH COVID-19 AND ACUTE PULMONARY EMBOLISM

251 Emergency Department Arrival by Ambulance for Patients Receiving a Pulmonary Embolism Diagnosis Is Associated With Hospitalization: Is Coming from Off-site Radiology an Exception?

251 Emergency Department Arrival by Ambulance for Patients Receiving a Pulmonary Embolism Diagnosis Is Associated With Hospitalization: Is Coming from Off-site Radiology an Exception?

Clinical outcomes and echocardiographic characteristics between African American and Caucasian patients with acute pulmonary embolism.

Despite socioeconomic disparities, no association between clinical presentation and poor outcomes explains a higher mortality in African Americans with pulmonary embolism (PE). The objective is to identify the co-morbidities and echocardiographic characteristics associated with increased mortality in African American patients. This is a cross-sectional study of Caucasian or African American patients with PE diagnosed between October 2015 and December 2017 at University of Maryland Medical Center. The outcomes were in-hospital death, length of stay, and bleeding. There were 303 African Americans and 343 Caucasians. Caucasians were older (p = 0.007), males (p = 0.01) with history of coronary artery revascularization (CABG (p = 0.001), coronary stents (p = 0.001)), trauma (p = 0.007), and/or recent surgeries (p = 0.0001). African Americans exhibited higher rates of diabetes (p = 0.01), chronic kidney disease (p = 0.0005), and smoking (p = 0.04). Severity of PE was similar between groups and there was no difference in clot burden size. African Americans had more right ventricular strain on Computer Tomography (p = 0.001) and echocardiogram (p = 0.004); also, underfilled left ventricles (p = 0.02) and higher right ventricular systolic pressures (p = 0.001). There was no difference in hospital mortality (7.1% vs. 7.9%, p = 0.71), length of stay (13.1 ± 16.7 vs 12.8 ± 14.9, p = 0.80) and bleeding (9.0% vs.8.3%. p = 0.72). Mortality was higher in African Americans who received advanced therapies (3.8% vs. 18.8%, p = 0.02). The risk of death increased with age (OR 1.04; 95%CI 1.020-1.073) and with advanced therapies (OR 2.43; 95%CI 1.029-5.769). Differences in co-morbidities, radiologic findings, and echocardiographic characteristics that may contribute to higher mortality in African American patients, specifically those receiving advanced therapies.

The Prognostic Significance of Pulmonary CT Angiography in Predicting the Outcomes of Acute Pulmonary Thromboembolism

Background: Pulmonary embolism (PE) is a potentially fatal condition. Knowledge of the prognostic factors for PE may facilitate the management of these patients. Pulmonary computed tomography (CT) angiography (PCTA) can play an effective role in their management. Objectives: To evaluate the prognostic value of certain PCTA-derived indicators of right ventricular dysfunction in patients with acute PE. Patients and Methods: A total of 61 hemodynamically stable patients with acute PE underwent PCTA and were followed-up for 60 days. The Qanadli index and 60-day mortality represented the PE severity and prognostic endpoints, respectively. The clinical significance of the following variables in predicting PE severity and mortality was examined: An abnormally positioned interventricular septum, right ventricular to left ventricular diameter ratio (RVD/LVD) on the axial plane, contrast medium reflux into the inferior vena cava (IVC), transverse diameter of the pulmonary trunk, and bolus-time curve indicators. Results: The 60-day mortality was estimated at 14.8% in this study. An abnormal interventricular septum morphology, RVD/LVD ratio, and contrast medium reflux into the IVC were significantly correlated with the Qanadli index. The pulmonary trunk diameter was the only predictor of 60-day mortality (optimal cutoff value, 33.5 mm; sensitivity, 66.7%; and specificity, 65.4%). The bolus-time curve indicators did not have any significant predictive value. Conclusion: Some PCTA-derived indicators of right ventricular dysfunction may serve as severity/prognostic predictors in hemodynamically stable patients with acute PE.

Association between CHA2DS2-VASc Score and Right Ventricular Dysfunction in Patients with Acute Pulmonary Embolism

Background: Acute right ventricular dysfunction (RVD) is a leading cause of death in the setting of acute pulmonary embolism (PE). Therefore, several studies investigated the predisposing factors of RVD. However, at present, little is known about the clinical predictors of RVD in the patients presented with acute PE.
 Objective: To assess the association of CHA2DS2-VASc Score with the PE severity, RVD and the in-hospital mortality in patients presented with acute PE.
 Methods: This study was conducted on 50 patients admitted with acute PE at Tanta University Hospitals. We studied the association of different variables including demographic data, common risk factors, clinical presentation, management and the in-hospital mortality with the PE clinical subgroups (massive, sub-massive and non-massive) based on the severity of clinical presentation and also the association of these variables with the thromboembolic risk (high, moderate and low) based on the CHA2DS2-VASc scores. The independent predictors of the RVD were then investigated by the univariate and multivariate regression analyses.
 Results: The massive PE presentation was associated with higher CHA2DS2-VASc scores (P value = 0.02). Also, the incidence of RVD was higher among the high risk group of patients (CHA2DS2-VASc scores ≥3) with P value = 0.009. TAPSE, MPI, FAC, and E`/A` ratio were found to be more significant in the high risk group (P value = 0.032, 0.002, 0.007 and 0.001), respectively. The independent predictors of RVD were demonstrated to be tachycardia, lower systolic blood pressure and CHA2DS2-VASc score (P value = 0.022, 0.007, 0.021), respectively. The CHA2DS2-VASc score predicted the presence of RVD with 66.7 % sensitivity and 78.6% specificity as demonstrated by the receiver operating characteristic (ROC) analysis, with area under the curve (AUC) of 0.776 (CI 0.636-0.882, P value < 0.001). This study demonstrated no statistically significant difference between the different risk groups regarding the in-hospital mortality.
 Conclusion: Being independent of other factors, the CHA2DS2-VASc score can be used as a new, simple, and reliable tool to predict the development of RVD in patients with acute PE.

Electrocardiography: an usefull tool for prediction of the diagnosis and severity of pulmonary embolism

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Pulmonary embolism (PE) is associated with morbidity and mortality. Immediate recognition of this condition is critical to commencement of early and appropriate therapy which could be lifesaving. Particularly in patients with suspected PE in which computed tomography pulmonary angiography (CTPA) is not promptly available or is contra-indicated, an electrocardiographic (ECG) score could serve as a ubiquitously available test to raise suspicion of PE. This study aimed to evaluate the diagnostic value of an ECG score for PE diagnosis. Methods Retrospective study of consecutive patients who performed CTPA in Emergency Department due to PE suspicion. All ECG were scored according to the previous published Daniel’s ECG score, by an investigator blinded for the CTPA result. Results The most common ECG findings in patients with PE were incomplete right-brand bock (48%), T wave inversion in DIII (48%), sinus tachycardia (41%) and Q wave in DII (31%). The S1Q3T3 sign was documented in 20% of patients. The ECG score was significantly higher in patients with PE compared to those without PE (5.06 vs 3.70, p=0.005). ECG score showed moderate accuracy to detect PE (AUC: 0.60; 95%CI: 0.53-0.67; p=0.004), but it is of a particular value because of very high specificity: an ECG score > 12 identified PE with a specificity of 96% (95% CI 91.93 – 98.38). The ECG score significantly increased the diagnostic accuracy of the diagnostic algorithm based on pretest clinical probability evaluated by Wells score combined with D-Dimer measurement (Wells & DD). In comparison to patients in which clinical pretest probability combined with D-dimer measurement considers PE excluded (Wells & ECG -), PE was 6.3 times more frequent in patients with Wells & DD +/ECG- (95% 2.7- 14.5) and 14.6 times more prevalent in the ones with Wells & DD +/ECG+ (95%CI: 4.1-51.3; p<0.001) – Figure 1. Conclusion In patients with clininal suspition of PE, na ECG score (Daniel’s score) >12 predicts PE with 96% specificity and could be used to increase the suspicion and define therapeutic strategy in patients in whom CTPA could not be immediately performed or is contra-indicated.

Sustainability of a Clinical Decision Support Intervention for Outpatient Care for Emergency Department Patients With Acute Pulmonary Embolism

Physicians commonly hospitalize patients presenting to the emergency department (ED) with acute pulmonary embolism (PE), despite eligibility for safe outpatient management. Risk stratification using electronic health record-embedded clinical decision support systems can aid physician site-of-care decision-making and increase safe outpatient management. The long-term sustainability of early improvements after the cessation of trial-based, champion-led promotion is uncertain. To evaluate the sustainability of recommended site-of-care decision-making support 4 years after initial physician champion-led interventions to increase outpatient management for patients with acute PE. This retrospective cohort study was conducted in 21 US community hospitals in an integrated health system. Participants included adult patients presenting to the ED with acute PE. Study sites had participated in an original decision-support intervention trial 4 years prior to the current study period: 10 sites were intervention sites, 11 sites were controls. In that trial, decision support with champion promotion resulted in significantly higher outpatient management at intervention sites compared with controls. After trial completion, all study sites were given continued access to a modified decision-support tool without further champion-led outreach. Data were analyzed from January 2019 to February 2020. ED treatment with a modified clinical decision support tool. The main outcome was frequency of outpatient management, defined as discharge home directly from the ED, stratified by the PE Severity Index. The safety measure of outpatient care was 7-day PE-related hospitalization. This study included 1039 patients, including 533 (51.3%) women, with a median (IQR) age of 65 (52-74) years. Nearly half (474 patients [45.6%]) were rated lower risk on the PE Severity Index. Overall, 278 patients (26.8%) were treated as outpatients, with only four 7-day PE-related hospitalizations (1.4%; 95% CI, 0.4%-3.6%). The practice gap in outpatient management created by the earlier trial persisted in the outpatient management for patients with lower risk: 109 of 236 patients (46.2%) at former intervention sites vs 81 of 238 patients (34.0%) at former control sites (difference, 12.2; [95% CI, 3.4-20.9] percentage points; P = .007), with wide interfacility variation (range, 7.1%-47.1%). In this cohort study, a champion-led, decision-support intervention to increase outpatient management for patients presenting to the ED with acute pulmonary embolism was associated with sustained higher rates of outpatient management 4 years later. The application of our findings to improving sustainability of practice change for other clinical conditions warrants further study.

Weakly supervised attention model for RV strain classification from volumetric CTPA scans

Background and objective: Evaluation of the right ventricle (RV) is a key component of the clinical assessment of many cardiovascular and pulmonary disorders. In this work, we focus on RV strain classification from patients who were diagnosed with pulmonary embolism (PE) in computed tomography pulmonary angiography (CTPA) scans. PE is a life-threatening condition, often without warning signs or symptoms. Early diagnosis and accurate risk stratification are critical for decreasing mortality rates. High-risk PE relies on the presence of RV dysfunction resulting from acute pressure overload. PE severity classification and specifically, high-risk PE diagnosis are crucial for appropriate therapy. CTPA is the golden standard in the diagnostic workup of suspected PE. Therefore, it can link between diagnosis and risk stratification strategies. Methods: We retrieved data of consecutive patients who underwent CTPA and were diagnosed with PE and extracted a single binary label of “RV strain biomarker” from the CTPA scan report. This label was used as a weak label for classification. Our solution applies a 3D DenseNet network architecture, further improved by integrating residual attention blocks into the network’s layers. Results: This model achieved an area under the receiver operating characteristic curve (AUC) of 0.88 for classifying RV strain. For Youden’s index, the model showed a sensitivity of 87% and specificity of 83.7%. Our solution outperforms state-of-the-art 3D CNN networks. The proposed design allows for a fully automated network that can be trained easily in an end-to-end manner without requiring computationally intensive and time-consuming preprocessing or strenuous labeling of the data. Conclusions: This current solution demonstrates that a small dataset of readily available unmarked CTPAs can be used for effective RV strain classification. To our knowledge, this is the first work that attempts to solve the problem of RV strain classification from CTPA scans and this is the first work where medical images are used in such an architecture. Our generalized self-attention blocks can be incorporated into various existing classification architectures making this a general methodology that can be applied to 3D medical datasets.

Prognostic factors of systemic lupus erythematosus patients with pulmonary embolism: An 11-year cohort study.

Systemic lupus erythematosus (SLE) patients have a higher risk of pulmonary embolism (PE) which is life-threatening, but there has been no research focusing on the prognosis of SLE patients with PE. This study was conducted to explore the prognostic factors of mortality in SLE patients with PE. In this observational cohort study, SLE inpatients with PE treated at Peking Union Medical College Hospital between January 2010 and December 2020 were included and age, gender, smoking history, the onset of SLE and PE, organ involvement, SLE disease activity index-2000 (SLEDAI-2K), severity of PE, and treatment regimen were collected. Kaplan-Meier survival curve and univariate and multivariate COX regression analysis were used to explore the prognostic factors of SLE patients with PE. A total of 86 SLE patients with PE were enrolled, with the age of 37.72±15.79 years old and the average lupus duration of 46.5 months. 17 patients (19.77%) died. 1- and 3-year survival rates were 83.40% and 79.40%. Thrombocytopenia (log-rank p = 0.004) and lymphocytopenia (log-rank p = 0.030) were predictors of mortality, and effective anticoagulation (log-rank p = 0.032), hydroxychloroquine (HCQ) (log-rank p = 0.021) were protective factors of mortality in SLE patients with PE. Effective anticoagulation was an independent protective factor of mortality in SLE patients with PE (HR = 0.14, p = 0.006). Patients with thrombocytopenia and lymphocytopenia are more likely to develop a poor prognosis. Effective anticoagulation and HCQ could improve the prognosis.

Clinical Manifestations and Diagnosis of Pulmonary Embolism in Routine Clinical Practice: Data from the Ryazan Regional Vascular Center

BACKGROUND: Data on the peculiarities of the clinical presentation and characteristics of pulmonary embolism (PE) and problems of its diagnosis in routine clinical practice (CP) are limited. Data obtained long ago are mostly described in terms of venous thromboembolism in general and practically do not include Russian patients with PE. The study was performed within the RusSIan REgistery of pulmoNAry embolism (SIRENA) register.
 AIM: To study the peculiarities of the clinical and demographic profile and diagnosis of PE in modern CP in comparison with the results of other PE registers.
 MATERIALS AND METHODS: In this registry-based study, medical records were analyzed to obtain information on the demographic profile, clinical presentation, and examination results of patients with PE (n = 107; age, 63 (5274) years; men, 39.3%) who received inpatient treatment in one of the Ryazan Regional Vascular centers. The study period was 13 months (20182019).
 RESULTS: The most common concomitant pathologies were arterial hypertension (70.1%), obesity (46.7%), and diabetes mellitus (17.8%). High- and moderate-risk factors were identified in 26.2% and 72.9% of the patients, respectively. Low-risk factors identified in 5.6% of the patients in different combinations did not have a single risk factor for PE development. Clinical manifestations included shortness of breath (93.5%), chest pain (43.0%), severe weakness (59.8%), tachycardia (29.0%), hypoxemia (27.1%), and unstable hemodynamics (18.7%). The most frequent electrocardiographic sign was a T-wave inversion in the right chest leads (52.3%). Right ventricle dysfunction was detected in 38.1% of the cases and elevation of troponin levels in 33.6%. According to the Pulmonary Embolism Severity Index scale, high- and very-high-risk cases accounted for 46.7% of the cases. According to the results of the integrated assessment of PE severity, 34.6% and 14.0% of the patients moved to the lower- and higher-risk classes, respectively. The proportion of moderate-risk cases increased from 23.4% to 62.6%, and the high- and very-high-risk cases reduced from 46.7% to 32.0%.
 CONCLUSION: The modern clinical picture of PE is characterized by a higher prevalence of concomitant pathology and reduction of the rates of traditional risk factors. There remain difficulties in PE diagnosis, which are associated with the concomitant pathology, absence of traditional risk factors, and non-specificity of the clinical manifestations and results of additional examinations.

Incidence and prognostic value of acute kidney injury in pulmonary embolism: data from the SIRENA registry

Aim. To evaluate the incidence and severity of acute kidney injury (AKI), as well as its ability to reclassify the risk of premature mortality and association with inhospital mortality in patients with pulmonary embolism (PE) in the Russian population.Material and methods. From April 2018 to April 2019, the SIRENA Russian Multicenter Registry included patients with PE, as well as the deceased, in whom the PE was detected by autopsy. AKI was diagnosed according to current KDIGO guidelines (2012). Creatinine calculated according to the MDRD equation and corresponding to a glomerular filtration rate of 75 ml/min/1,73 m2 (baseline) was taken as the initial one, with subsequent assessment relative to the parameter value upon admission. The risk stratification of early death was carried out in accordance with the current ESC clinical guidelines (2019).Results. A total of 604 patients with PE were examined (men — 293 (49%), women — 311 (51%), mean age — 64±15 years). AKI was diagnosed in 223 (37%) of them. Stage 1 AKI was detected in 146 (65%), 2 — in 55 (25%), 3 — in 22 (10%) patients. Prior chronic kidney disease was recorded in 61 (10%) patients. Seventy-one (12%) patients had a high risk of death, 364 (61%) — intermediate risk, and 164 (27%) — low risk. The AKI incidence increased as the severity of PE increased: at low risk of death — 26%, intermediate — 38%, high — 59% (p<0,0001). In total, 107 (18%) patients died in the hospital. AKI led to an increase in mortality within following risk groups: at low risk, this effect was a trend (6 (5%) vs 6 (14%); p=0,052); at intermediate and high risk, significant differences was obtained (30 (13%) vs 41 (30%), p<0,001; 4 (14%) vs 19 (45%), p=0,006, respectively). Multivariate Cox regression demonstrated that AKI is a predictor of inhospital death (odds ratio (OR), 3,66 (95% confidence interval (CI): 2,37-5,66; p<0,0001), regardless of increased troponin levels (OR, 1,31 (95% CI: 0,80-2,14; p=0,28) and right ventricular dysfunction (OR, 1,23 (95% CI: 0,74-2,04; p=0,42).Conclusion. Thirty-seven percent of Russian patients with PE have AKI diagnosed by baseline creatinine. In 2/3 of the examined patients, stage 1 AKI is observed. The AKI incidence increases as the severity of PE increases. The presence of AKI reclassifies patients into a higher risk category for death and is associated with a significant increase in inhospital mortality.

The Prognostic Value of C-Reactive Protein/Albumin Ratio in Acute Pulmonary Embolism.

Serum C-reactive protein (CRP) to albumin ratio (CAR) has been defined as an inflammation-based prognostic marker. We evaluated the association and prognostic value of CRP/albumin ratio in patients with pulmonary embolism (PE). A total of 256 patients with acute PE who were hospitalized between March 2016 and December 2020 were retrospectively reviewed. PE severity index (PESI) was calculated. Serum levels of CRP and albumin that were obtained at the time of admission were used for calculation. CAR was evaluated for correlation with PESI, and thus, foresee the risk of death due to PE. There were 186 patients eligible for inclusion. 54 patients were in intermediate, 34 patients were in high risk and 98 patients were in very high-risk group according to PESI score. In the correlation analysis, we observed moderate positive correlations between CRP/albumin ratio, troponin and PESI score (r = 0.584, p < 0.0001; r = 521, p < 0.0001, respectively). Regression analysis revealed that only CRP/albumin ratio and PESI score were independent risk factors associated with 6-month mortality of acute PE patients. The AUC for CRP/albumin ratio was 0.643, 0.751, and 0.763 for 30-day, 90-day, and 6-month mortality, respectively (95% CI: 0.550-0.737, 0.672-0.830, 0.687-0.838]. A cut-off value of 5.33 for CRP/albumin ratio was associated with 65.3% sensitivity and 65.6% specificity in predicting 6-month mortality. The CRP/albumin ratio, an inexpensive and easily measurable laboratory variable, may be a useful prognostic marker of PE, especially when other causes that alter serum levels are excluded from the study.

An efficient and fast multi-band focused bioimpedance solution with EIT-based reconstruction for pulmonary embolism assessment: a simulation study from massive to segmental blockage

Objective. Pulmonary embolism (PE) is an acute condition that blocks the perfusion to the lungs and is a common complication of Covid-19. However, PE is often not diagnosed in time, especially in the pandemic time due to complicated diagnosis protocol. In this study, a non-invasive, fast and efficient bioimpedance method with the EIT-based reconstruction approach is proposed to assess the lung perfusion reliably. Approach. Some proposals are presented to improve the sensitivity and accuracy for the bioimpedance method: (1) a new electrode configuration and focused pattern to help study deep changes caused by PE within each lung field separately, (2) a measurement strategy to compensate the effect of different boundary shapes and varied respiratory conditions on the perfusion signals and (3) an estimator to predict the lung perfusion capacity, from which the severity of PE can be assessed. The proposals were tested on the first-time simulation of PE events at different locations and degrees from segmental blockages to massive blockages. Different object boundary shapes and varied respiratory conditions were included in the simulation to represent for different populations in real measurements. Results. The correlation between the estimator and the perfusion was very promising (R = 0.91, errors <6%). The measurement strategy with the proposed configuration and pattern has helped stabilize the estimator to non-perfusion factors such as the boundary shapes and varied respiration conditions (3%–5% errors). Significance. This promising preliminary result has demonstrated the proposed bioimpedance method’s capability and feasibility, and might start a new direction for this application.

Acute Pulmonary Embolism: Prognostic Role of Computed Tomography Pulmonary Angiography (CTPA).

Computed Tomography Pulmonary Angiography (CTPA) is considered the gold standard diagnostic technique in patients with suspected acute pulmonary embolism in emergency departments. Several studies have been conducted on the predictive value of CTPA on the outcomes of pulmonary embolism (PE). The purpose of this article is to provide an updated review of the literature reporting imaging parameters and quantitative CT scores to predict the severity of PE.

Pulmonary embolism severity and in-hospital mortality: An international comparative study between COVID-19 and non-COVID patients

ObjectiveTo compare the severity of pulmonary embolism (PE) between patients with and without COVID, and to assess the association between severity and in-hospital-mortality. MethodsWe performed an analysis of 549 COVID (71.3% PCR-confirmed) and 439 non-COVID patients with PE consecutively included by 62 Spanish and 16 French emergency departments. PE-severity was assessed by size, the presence of right ventricular dysfunction (RVD), and the sPESI. The association of PE-severity and in-hospital-mortality was assessed both in COVID and non-COVID patients, and the interaction of COVID status and PE severity/outcome associations was also evaluated. ResultsCOVID patients had PEs of smaller size (43% vs 56% lobar or larger, 42% vs. 35% segmental and 13% vs. 9% subsegmental, respectively; p = 0.01 for trend), less RVD (22% vs. 16%, p =0.02) and lower sPESI (p =0.03 for trend). Risk of in-hospital death was higher in COVID patients (12.8% vs. 5.3%, p < 0.001). PE-severity assessed by RVD and sPESI was independently associated with in-hospital-mortality in COVID patients, while PE size and sPESI were significantly associated with in-hospital-mortality in non-COVID. COVID status showed a significant interaction in the association of PE size and outcome (p =0.01), with OR for in-hospital mortality in COVID and non-COVID patients with lobar or larger PE of 0.92 (95%CI=0.19–4.47) and 4.47 (95%CI=1.60–12.5), respectively. Sensitivity analyses using only PCR-confirmed COVID cases confirmed these results. ConclusionCOVID patients present a differential clinical picture, with PE of less severity than in non-COVID patients. An increased sPESI was associated with the risk of mortality in both groups but, PE size did not seem to be associated with in-hospital mortality in COVID patients.