Pulmonary Embolism In Patients Research Articles

Increased risk of pulmonary embolism in patients with dermatomyositis/polymyositis, a retrospective cohort study from Israel

BackgroundDespite the well-established association between chronic inflammatory conditions and pulmonary embolism(PE), previous investigations of the relationship between Dermatomyositis(DM) and Polymyositis(PM) with PE were scarce and have been subject to significant limitations, including small sample sizes and failure to account for potential confounders. ObjectivesTo investigate the correlation between DM/PM and PE, as well as assessing the impact of serologic status, myonecrosis, and inflammation markers on this relationship. MethodsIn this large, nationwide population-based study, we used the Clalit Health Services medical database and extracted all DM/PM patients who were first diagnosed between 1 January 2002 to 31 December 2018 and compared them with age and gender matched controls in a ratio of 1:5. Serological and laboratory values were obtained for each patient. Rates of PE were compared between groups using multivariate models. ResultsThe study included 1557 DM patients with 7633 controls, and 528 PM patients with 2560 controls. Compared with matched controls, the rates of PE were significantly higher in the DM/PM group, PM patients(2.8 % vs 0.5 % in controls, OR = 5.73, p < 0.001), DM patients(1.2 % vs 0.3 % in controls, OR = 3.42, p < 0.001). APLA seropositivity was significantly more prevalent in DM/PM patients compared with their matched controls, PM patients(10.8 % vs 2.7 % in controls, p < 0.001), DM patients(7.9 % vs 1.6 % in controls, p < 0.001). APLA seropositivity had a synergistic effect for PE in the DM/PM(OR = 23.18, p < 0.001). ConclusionsDM and PM are associated with higher rates of PE. Furthermore, patients with DM/PM demonstrate a significantly higher prevalence APLA which act as a potentiator of thrombosis in these patients.

Large-bore Mechanical Thrombectomy Versus Catheter-directed Thrombolysis in the Management of Intermediate-risk Pulmonary Embolism: Primary Results of the PEERLESS Randomized Controlled Trial.

There is a lack of randomized controlled trial (RCT) data comparing outcomes of different catheter-based interventions for intermediate-risk pulmonary embolism (PE). PEERLESS is a prospective, multicenter, RCT that enrolled 550 intermediate-risk PE patients with right ventricular dilatation and additional clinical risk factors randomized 1:1 to treatment with large-bore mechanical thrombectomy (LBMT) or catheter-directed thrombolysis (CDT). The primary endpoint was a hierarchal win ratio (WR) composite of the following: 1) all-cause mortality, 2) intracranial hemorrhage, 3) major bleeding, 4) clinical deterioration and/or escalation to bailout, and 5) postprocedural intensive care unit (ICU) admission and length of stay, assessed at the sooner of hospital discharge or 7 days post-procedure. Assessments at the 24-hour visit included respiratory rate, mMRC dyspnea score, NYHA classification, right ventricle (RV)/left ventricle (LV) ratio reduction, and RV function. Endpoints through 30 days included total hospital stay, all-cause readmission, and all-cause mortality. The primary endpoint occurred significantly less frequently with LBMT vs CDT (WR 5.01 [95% CI: 3.68-6.97]; P<0.001). There were significantly fewer episodes of clinical deterioration and/or bailout (1.8% vs 5.4%; P=0.04) with LBMT vs CDT and less postprocedural ICU utilization (P<0.001), including admissions (41.6% vs 98.6%) and stays >24 hours (19.3% vs 64.5%). There was no significant difference in mortality, intracranial hemorrhage, or major bleeding between strategies, nor in a secondary WR endpoint including the first 4 components (WR 1.34 [95% CI: 0.78-2.35]; P=0.30). At the 24-hour visit, respiratory rate was lower for LBMT patients (18.3±3.3 vs 20.1±5.1; P<0.001) and fewer had moderate to severe mMRC dyspnea scores (13.5% vs 26.4%; P<0.001), NYHA classifications (16.3% vs 27.4%; P=0.002), and RV dysfunction (42.1% vs 57.9%; P=0.004). RV/LV ratio reduction was similar (0.32±0.24 vs 0.30±0.26; P=0.55). LBMT patients had shorter total hospital stays (4.5±2.8 vs 5.3±3.9 overnights; P=0.002) and fewer all-cause readmissions (3.2% vs 7.9%; P=0.03), while 30-day mortality was similar (0.4% vs 0.8%; P=0.62). PEERLESS met its primary endpoint in favor of LBMT vs CDT in treatment of intermediate-risk PE. LBMT had lower rates of clinical deterioration and/or bailout and postprocedural ICU utilization compared with CDT, with no difference in mortality or bleeding.

Clinical outcomes of edoxaban treatment without parenteral anticoagulation therapy for acute venous thromboembolism: Insight from the COMMAND VTE Registry-2

Abstract Background Direct oral anticoagulants (DOACs) including edoxaban are currently widely used all over the world. Each DOAC has a specific usage for the treatment and second prevention of venous thromboembolism (VTE) in the acute phase as well as in the chronic phase. Edoxaban is recommended to be administered after an appropriate initial treatment including parenteral anticoagulation therapy such as heparin. However, because of the rapid anticoagulant effect of edoxaban after oral intake, some physicians could administer edoxaban initially without parenteral anticoagulation therapy in the daily clinical practice, which has not been investigated so far. Purpose The purpose of this study is to explore the effectiveness and safety of edoxaban treatment for VTE without initial parenteral anticoagulation therapy. Methods The COMMAND VTE Registry-2 is a multicenter registry enrolling 5,197 consecutive acute symptomatic VTE patients among 31 centers in Japan between January 2015 and August 2020. Of those, 1842 patients received edoxaban including 848 patients with pulmonary embolism (PE) and 994 patients with deep vein thrombosis (DVT) alone, who were divided into 2 groups based on the presence or absence of initial parenteral anticoagulation therapy with heparin. Propensity score matching (PSM) was performed to adjust for potential baseline differences in the 2 groups. Results PE and DVT patients with initial parenteral anticoagulation therapy with heparin accounted for 623 (73.5%) and 244 (24.5%), respectively. After the PSM, 195 pairs of PE patients and 226 pairs of DVT patients were matched. In PE patients, those matched by the PSM were relatively mild cases compared to the unmatched cases (simplified PESI score=0: 25.9% vs. 12.4%, P&amp;lt;0.001). Whereas, in DVT patients, those matched were relatively severe cases compared to unmatched cases (isolated distal DVT: 24.1% vs. 71.0%, P&amp;lt;0.001). In the matched cohort, there was no significant difference in baseline characteristics between the 2 groups, including simplified PESI score in PE patients and thrombus location profile in DVT patients. In both PE patients and DVT patients, the 30-day cumulative incidences of all-cause death were not significantly different between the 2 groups (PE patients: 3.7% vs. 2.6%, P=0.56; DVT patients: 2.7% vs. 4.5%, P=0.31). Similarly, the 30-day cumulative incidences of recurrent VTE and major bleeding were not significantly different between the 2 groups (recurrent VTE: PE patients: 0% vs. 0.5%, P=0.32; DVT patients: 0.6% vs. 0.9%, P=0.99; major bleeding: PE patients: 1.5% vs. 3.2%, P=0.32; DVT patients: 2.2% vs. 3.2%, P=0.54) Conclusion In this current real-world VTE registry, a certain number of patients received edoxaban without parenteral anticoagulation therapy, who did not show a signal of worse clinical outcomes.

Investigating the Relationship Between Demographic and Laboratory Factors with the Incidence of PTE in COVID-19

Background: In 2019, after the first case was discovered in Wuhan, China, the COVID-19 virus began to spread rapidly across the world, leading the WHO to declare the disease a public health emergency. Objectives: Thromboembolism refers to the formation of a clot in a vein, which then travels through the vascular system, potentially blocking blood flow in another location. Methods: This retrospective cohort study aimed to investigate the risk factors for pulmonary embolism in COVID-19 patients hospitalized at Firoozabadi Hospital from May to the end of December 2020. After extracting the required information, the data was entered into SPSS version 26 software for analysis. Results: In total, data from 283 COVID-19 patients admitted to Firouzabadi Hospital in Tehran in 2020 were collected. The average age of the patients was 58.8 ± 15.9 years. Among the 283 patients, 162 (57.6%) were male, 79 patients (27.9%) had pulmonary embolism, 102 patients (36%) were smokers, and 107 patients (37.8%) had a history of hypertension. A significant relationship was observed between the occurrence of pulmonary embolism and elevated levels of, white blood cells (WBC) (P = 0.0001), lactate dehydrogenase (LDH) (P = 0.0001), D-dimer (P = 0.0001), polymorphonuclear neutrophils (PMN) (P = 0.020), lymphocytes (P = 0.013), alkaline phosphatase (Alk.P) (P = 0.025), alanine aminotransferase (ALT) (P = 0.019), and aspartate aminotransferase (AST) (P = 0.017). Conclusions: Based on the results of this study, the incidence of pulmonary embolism in hospitalized COVID-19 patients who underwent CT angiography due to clinical suspicion of thrombosis was 27.9%. Additionally, factors such as smoking, a previous history of pulmonary thromboembolism, high WBC, elevated liver function tests (LFT), and elevated LDH levels were identified as risk factors for the occurrence of pulmonary embolism in these patients.

Baseline characteristics, management patterns and outcome in patients with pulmonary embolism and malignancy: Insights from a single-centre study

Abstract Background and aim The presence of malignancy is an important factor that increases the risk of venous thromboembolism. On the other hand, acute pulmonary embolism (PE) is one of the main causes of death in this setting. In this study, we evaluated the impact of active malignancy on the treatment choices, and short and long term clinical outcomes in patients with acute PE. Methods In this study conducted in a tertiary center, 872 acute PE patients (age 61.6±16.8 years, female 57.5 %) from different risk categories were treated with thrombolytic, anticoagulant and catheter-based therapies in accordance with currently available acute PE guidelines. The population was retrospectively analyzed and divided into two groups according to the presence of active malignancy. Results Active malignancy was documented in 129 (14.8 %) patients. In the groups with and without malignancy, the proportions of low-, intermediate-low-, intermediate-high-, and high-risk PE patients were 3.1 % vs. 15.6 %, 17.8 % vs. 16.7 %, 60.5 % vs. 60 %, and 18.6 % vs. 7.7 %, respectively (p&amp;lt;0.001). While the two groups did not differ in terms of echocardiographic and computed tomographic pulmonary angiography (CTPA) characteristics, the presence of contraindications for thrombolytic were more frequent in the malignancy group (22.5% vs. 10.9%, p&amp;lt;0.001). Ultrasound-assisted thrombolysis (USAT), rheolytic thrombectomy (RT), systemic thrombolysis (ST) and anticoagulation-alone (AC) therapies were noted in 27.3 %, 6.4 %, 6.4 % and 49.7 % of overall PE patients. The RT and AC therapies were more frequent in PE patients with malignancy whereas ST and USAT were more frequently used in the absence of malignancy. Notably, lytic dosages and treatment durations in USAT and ST protocols were comparable between malignant and non-malignant PE cohorts. Regardless of the presence of malignancy and the treatment modality chosen, significant improvements were achieved in the clinical, echocardiographic and CTPA measures of the PE severity (p&amp;lt;0.001 for all). Major and minor bleeding rates were also similar in both groups, while in-hospital and, as expected, long-term mortality were higher in the malignancy cohort. Active malignancy and PESI score were found to be independent predictors for composite end-point of 60-day mortality and PE-related rehospitalization (adjusted odds ratio (OR): 2.43; 95 % CI: 1.32 - 4.47, p=0.04) and (OR: 1.02; 95 % CI: 1.01-1.01, p&amp;lt;0.001), respectively. Malignancy (OR: 3.5, 95 % CI: 2.15-5.75, p&amp;lt; 0.001) and chronic obstructive pulmonary disease (OR: 2.51, 95 % CI: 1.35-4.68, p&amp;lt; 0.003) were independent predictors of long-term mortality. Conclusion Concomitant malignancy adversely affects both short- and long-term outcomes in patients with acute PE. Although these patients are more vulnerable, it is possible to achieve satisfactory treatment success with acceptable bleeding rates with the inclusion of catheter-based methods as treatment option.Survival plot

Catheter-directed treatment in acute pulmonary embolism

Abstract Background Pulmonary embolism (PE) is a potentially life-threatening emergency. PE occurs when venous thrombi embolize to the pulmonary circulation, resulting in vascular occlusion, impairing gas exchange and circulation. Initial risk stratification of acute PE is based on clinical symptoms, cardiac adaptations, comorbidities, and, in particular signs of haemodynamic instability. The primary aim of the treatment is to restore blood flow to the affected areas of the lungs, resolving/removing embolus burden and preventing further clot formation. In patients with severe PE, comprising decompensation or intended hemodynamic compromise, immediate reperfusion is recommended. Catheter-directed therapies (CDT) are an innovative treatment option for patients with severe PE to resolve embolus and restore pulmonic perfusion. These procedures are less invasive and are supposed to have a lower risk of bleeding complications compared to systemic thrombolysis or surgical embolectomy. Recent studies have shown that CDT are safe and effective treatment options for PE. Purpose Nevertheless, CDT have to demonstrate their non-inferiority and benefits regarding patients’ outcomes in real-world settings. Methods The German nationwide inpatient sample was used to identify and include all hospitalizations of patients with PE 2005-2020 in Germany. PE patients were stratified for use of CDT. Temporal trends of the usage and the impact of CDT on case-fatality and other outcomes were investigated (source: RDC of the Federal Statistical Office and the Statistical Offices of the federal states, DRG Statistics 2005-2020, own calculations). Results Overall, 1,373,084 hospitalisations of patients with PE (55.9% aged ≥70 years; 53.0% females) were included in this study 2005-2020. Among these, 427,238 (31.1%) were categorized as severe PE and 3330 (0.2%) were treated with CDT with an annual increase from 0.17% (2005) to 0.51% (2020). PE patients of younger age, male sex, with previous surgery, and with severe PE were more often treated with CDT. In patients with severe PE, CDT was attributed to lower MACCE (28.2% vs. 34.2%, P&amp;lt;0.001) and in-hospital case-fatality rate (24.9% vs. 31.0%, P&amp;lt;0.001), but higher prevalence of major bleeding (29.5% vs. 17.5%, P&amp;lt;0.001). CDT was associated with reduced MACCE (OR 0.91 [95%CI 0.83-0.99], P=0.031), a trend towards lower case-fatality (OR 0.92 [95%CI 0.84-1.01], P=0.068), but increased major bleeding (OR 2.12 [95%CI 1.92-2.33], P&amp;lt;0.001) in severe PE. The benefit of CDT regarding case-fatality was age-dependent, with the largest benefit in the 8th and 9th decade of life. Conclusions Although the annual rate of CDT increased from 2005 to 2020 in Germany, only 0.2% of the PE patients were treated with CDT. Selection criteria for CDT treatment were younger age, male sex, previous surgery, and severe PE. CDT treatment was associated with reduced MACCE and case-fatality rate in PE patients with severe PE.

Interleukin 21, plasminogen activator inhibitor 1 and fractalkine improve risk stratification in elderly patients with pulmonary embolism

Abstract Background The importance of clinical parameters for predicting short-term mortality in hemodynamically stable patients with pulmonary embolism (PE) is acknowledged within the Pulmonary Embolism Severity Index (PESI) Score. Little is known about the value of novel biomarkers in this context. Given the pathophysiology of PE, markers related to inflammation and thrombosis, such as interleukin 21 (IL-21), fractalkine and plasminogen activator inhibitor 1 (PAI1) are of particular interest. Purpose To identify new protein biomarkers that improve 90d mortality prediction compared to the PESI score in elderly PE patients. Methods 1003 patients with venous thromboembolism aged ≥65 years were recruited between 2009 and 2011 from 9 hospitals in Switzerland (SWITCO65+ cohort). Among these, 778 patients were excluded due to missing data, deep venous thrombosis only, blood sample taken &amp;gt;1 day after diagnosis, no initial anticoagulation, systolic blood pressure &amp;lt;90 mmHg, withdrawal within 1 day or denying further use of data; 225 patients were prospectively included. Outcome was independently adjudicated up to 1 year after the index event. To identify candidate proteins, untargeted proteomic analyses (OLINK) were conducted in cases with 90d all-cause mortality (n=20) matched 1:2 (age, sex) to controls without events (n=40). 26 candidate proteins were then validated in all 225 PE patients using ELISA and Mesoscale analyses. Using ROC analyses, the most promising proteins to predict death within 90d were identified within this cohort. Optimal biomarker cut-off levels were derived using the Youden Index and survival analyses were computed. To evaluate the predictive value of these biomarkers, hazard ratios (HR) were calculated after adjusting for age, sex, and BMI. AUC-ROC analyses were performed to assess the biomarkers’ value for risk prediction compared to the PESI score. Results Baseline characteristics (Figure 1) did not differ between patients who died within 90d and those who did not, except for median PESI score (108 [95 – 125] vs. 87 [79 – 101], p&amp;lt;0.001). Optimal biomarker cut-off values were: IL-21: 56.17pg/ml, PAI1: 36.82pg/ml, fractalkine: 66’515pg/ml. Increased levels of IL-21 and PAI1 were associated with increased mortality (HR IL-21 = 1.5 [95% CI: 0.99 - 2.79], HR PAI1 = 2.6 [95% CI: 1.7 – 4.8]), whereas patients with elevated fractalkine levels were at lower risk to die within 90d (HR fractalkine = 0.37 [95% CI: 0.16 - 0.60]). For prediction of 90d mortality, the three assessed biomarkers showed a higher AUC than the PESI score. Combining the PESI score with the biomarkers did not further improve the AUC (Figure 2). Conclusions The protein biomarkers IL-21, PAI1 and fractalkine improve prediction of 90d mortality in elderly, hemodynamically stable PE patients compared to the PESI score. These biomarkers highlight the contribution of inflammation and thrombosis in the pathophysiology of PE and warrant further investigation.Baseline CharacteristicsROC Curves for Biomarkers and PESI Score

Lower early mortality after acute pulmonary embolism in patients with WHO-defined obesity: results from a post-hoc cohort analysis with external validation

Abstract Background The relationship between obesity, defined as a Body Mass Index (BMI) ≥ 30 kg/m2, and mortality in venous thrombo-embolism remains controversial. Objectives To compare early outcomes after pulmonary embolism (PE) between obese patients, and non-obese, non-underweight patients. Methods We performed a post-hoc analysis based on prospectively recorded individual patient data from the multicenter BFC-FRANCE registry. We compared rates of outcomes using multivariable logistic regression or a Cox model for 30-day and 6-month outcomes respectively. We assessed the incremental value of adding BMI information on top of the 30-day European Society of Cardiology (ESC) prognostic algorithm. Results A total of 2,390 patients with a BMI ≥ 18.5 kg/m2 (mean age, 66.9±16.8 years; 1,188 men [49.7%]) were included, 686 patients [28.7%] in the obese group, and 1,704 patients [71.3%] in the non-obese group. Mortality rates were significantly lower in obese patients versus non-obese patients at 30 days (OR, 0.59; 95% CI, 0.35-0.98), and 6 months. Cox-model-derived adjusted curves for all-cause death at 6 months, with hazard ratios (HRs) between obese and non-obese patients, after acute PE, are shown in the Figure. Rates of secondary non-fatal outcomes (including recurrent VTE) did not differ between groups. The addition of the obesity information on top of the ESC prognostic model improved global model fit, and discriminatory and calibration capacities, yielding significant reclassification based on the observed mortality rates with the ESC model as reference. Findings were confirmed in an external validation using 35,796 PE patients from the RIETE registry. Conclusion We present evidence indicating lower early and mid-term mortality after PE in patients classified as obese based on BMI, compared with non-obese, non-underweight patients. BMI should likely be incorporated into algorithms or scoring systems for predicting early mortality following PE.

The efficacy and safety of thrombolytic therapy for acute pulmonary embolism in patients with active malignant disease

Abstract Background Active malignant disease is associated with pulmonary embolism and the treatment of this condition is very challenging. The efficacy and safety of thrombolytic therapy for acute severe PE in patients with active malignant disease is unknown. Aim This study aimed to investigate hospital mortality rate and the incidence of major bleeding at 7 days according to the International Society of Thrombosis and Hemostasis (ISTH) criteria in patients with active malignant disease who were treated with thrombolytic therapy due to severe acute PE. Methods Patients with acute PE proven by computed tomography pulmonary angiography who were admitted to intensive care units have enrolled in the Regional PE Registry (REPER) since 2015, consisting of 10 hospitals from the 4 east Balkan countries. The decision to use thrombolytic therapy was at the discretion of the attending physicians, and it was used in high-risk, and intermediate-high-risk PE patients. Hospital mortality and the incidence of major bleeding at 7 days were compared between patients with active cancer and those without it who received thrombolytic therapy. Alteplase-based therapy was used. Results Among 2070 patients with acute PE enrolled in REPER, intermediate-high and high-risk PE had 795 patients without malignant disease and 135 had active malignant disease in the last 6 months. Patients with malignant disease had less chance to be treated with thrombolysis than patients without it (29.1% vs 44.7%, OR 0.508, 95%CI 0.341-0.756, p=0.001). For patients treated with thrombolysis, hospital mortality was non significantly higher in patients with the malignant disease compared to patients without it (25.6% vs 16,1%, OR 1.803, 95%CI 0.833-3.904, p=0.132), and the incidence of major bleeding at seven days was similar (15.4% vs 18.5%, OR 0.800, 95%CI 0.322-1.989, p=0.6131). There was no significant difference in age, sex, and PE risk distribution between patients with active malignant disease and those without it who were treated with thrombolysis. Conclusion Thrombolytic therapy seems to be underutilized in patients with the active malignant disease compared to patients without it in severe acute PE. In the selected patients who were treated with thrombolysis for severe acute PE, the efficacy and safety are similar between patients with and without active malignant disease.

Intracranial haemorrhage following treatment for pulmonary embolism: analysis of the german nationwide inpatient sample

Abstract Background Intracranial haemorrhage (ICH) can be a life-threatening complication of pulmonary embolism (PE) and its treatment during the acute phase. Purpose To characterize patients hospitalized with PE and ICH by identifying risk factors across different treatment groups, and to detect temporal trends in a large nationwide sample. Methods The German nationwide inpatient sample was screened for patients admitted with PE during the period 2005-2020. All hospitalizations were stratified based on the occurrence of ICH and accordingly, risk factors for ICH were investigated (source: Research data center [RDC] of the Federal Statistical Office and the Statistical Offices of the federal states, DRG Statistics 2005-2020, own calculations). Results Overall, 816,653 hospitalizations were included in the present study; among them, 2516 (0.3%) experienced an ICH event and 84,810 (10.4%) died in-hospital. The annual number of hospitalizations of patients admitted due to PE increased steadily from 38,749 in 2005 to 54,966 in 2020, whereas the incidence of ICH remained, despite annual fluctuations, largely stable over time, both in the entire study population and in the subgroup of patients with severe PE as defined by clinical and haemodynamic parameters (n=270,980 [33.2%]). ICH was overall more frequent after the seventh decade of life but, interestingly, no correlation with age was found amongst patients with severe PE (Figure 1). ICH in hospitalized PE patients was associated with an aggravated comorbidity burden mirrored by a higher Charlson Comorbidity Index (5.0 [interquartile range 4.0-7.0] vs. 4.0 [2.0-5.0], P&amp;lt;0.001). This was mainly driven by the higher prevalence of heart failure (27.3% vs. 19.4%, P&amp;lt;0.001) and acute or chronic kidney disease (27.6% vs. 18.1%, P&amp;lt;0.001) in patients with ICH. In addition, severe PE (OR 3.09 [95% CI 2.84-3.35], P&amp;lt;0.001), acute kidney injury (OR 3.60 [3.09-4.18], P&amp;lt;0.001), and particularly ischaemic stroke (OR 14.64 [12.61-17.00], P&amp;lt;0.001) were identified as independent predictors of ICH by multivariable logistic regressions. Overall, 27% of the ICH cases were related to systemic thrombolysis. In PE patients treated with systemic thrombolysis, age ≥70 years as well as female sex were independent predictors of ICH. Finally, ICH was independently associated with a substantial increase in case-fatality in patients hospitalized with PE (univariate OR: 5.38 [4.97-5.84], P&amp;lt;0.001; multivariable OR: 6.16 [5.64-6.72], P&amp;lt;0.001). Conclusions In this healthcare dataset of the German nationwide inpatient sample, the overall incidence of ICH remained low at 0.3% over the 15-year study period. Severe PE, age, comorbidity burden, kidney disease, heart failure and ischaemic stroke were independent risk factors for ICH.

Cardiovascular comorbidities and risk stratification in normotensive acute pulmonary embolism patients with right ventricular dysfunction and normal cardiac troponin: insights from a regional registry

Abstract Background Acute pulmonary embolism (PE) management guidelines categorize normotensive patients with right ventricle dysfunction (RVD) and normal cardiac troponin (cTn) as intermediate low risk. This study explores the prevalence of cardiovascular comorbidities and their impact on risk stratification in this specific cohort. Purpose To investigate the characteristics of normotensive acute PE patients with RVD and normal cTn, emphasizing the role of pre-existing cardiovascular diseases in determining the intermediate-low risk status. Methods A total of 1675 PE patients from a regional registry were screened, excluding high-risk and intermediate-high-risk cases. Among the remaining 400 normotensive patients with RVD, 353 with echocardiography and normal cTn were included. Patients were categorized into low or intermediate-low risk based on RVD presence. Cardiovascular comorbidities were assessed, and logistic regression analyzed their association with intermediate-low risk. Results Intermediate-low-risk patients (n=137) exhibited significantly higher rates of chronic heart failure, arterial hypertension, coronary artery disease, diabetes, and atrial fibrillation compared to low-risk patients (n=216). A substantial 77.4% of intermediate-low-risk patients had at least one cardiovascular comorbidity, significantly elevating the risk of RV dysfunction (adjusted OR 2.954, p&amp;lt;0.001). The all-cause hospital mortality was 5.1% in intermediate-low-risk and 1.4% in low-risk PE. Conclusions Normotensive acute PE patients with RVD and normal cTn are predominantly burdened with chronic cardiovascular conditions. The majority of intermediate-low-risk patients have at least one cardiovascular comorbidity, indicating an increased risk of death during hospitalization compared to low-risk patients. This study underscores the necessity for nuanced risk stratification considering pre-existing cardiovascular diseases for tailored and effective management. These findings have important implications for optimizing treatment strategies and improving outcomes in this high-risk population.

Quantitative texture analysis using machine learning for predicting interpretable pulmonary perfusion from non-contrast computed tomography in pulmonary embolism patients

BackgroundPulmonary embolism (PE) is life-threatening and requires timely and accurate diagnosis, yet current imaging methods, like computed tomography pulmonary angiography, present limitations, particularly for patients with contraindications to iodinated contrast agents. We aimed to develop a quantitative texture analysis pipeline using machine learning (ML) based on non-contrast thoracic computed tomography (CT) scans to discover intensity and textural features correlated with regional lung perfusion (Q) physiology and pathology and synthesize voxel-wise Q surrogates to assist in PE diagnosis.MethodsWe retrospectively collected 99mTc-labeled macroaggregated albumin Q-SPECT/CT scans from patients suspected of PE, including an internal dataset of 76 patients (64 for training, 12 for testing) and an external testing dataset of 49 patients. Quantitative CT features were extracted from segmented lung subregions and underwent a two-stage feature selection pipeline. The prior-knowledge-driven preselection stage screened for robust and non-redundant perfusion-correlated features, while the data-driven selection stage further filtered features by fitting ML models for classification. The final classification model, trained with the highest-performing PE-associated feature combination, was evaluated in the testing cohorts based on the Area Under the Curve (AUC) for subregion-level predictability. The voxel-wise Q surrogate was then synthesized using the final selected feature maps (FMs) and model score maps (MSMs) to investigate spatial distributions. The Spearman correlation coefficient (SCC) and Dice similarity coefficient (DSC) were used to assess the spatial consistency between FMs or MSMs and Q-SPECT scans.ResultsThe optimal model performance achieved an AUC of 0.863 during internal testing and 0.828 on the external testing cohort. The model identified a combination containing 14 intensity and textural features that were non-redundant, robust, and capable of distinguishing between high- and low-functional lung regions. Spatial consistency assessment in the internal testing cohort showed moderate-to-high agreement between MSMs and reference Q-SPECT scans, with median SCC of 0.66, median DSCs of 0.86 and 0.64 for high- and low-functional regions, respectively.ConclusionsThis study validated the feasibility of using quantitative texture analysis and a data-driven ML pipeline to generate voxel-wise lung perfusion surrogates, providing a radiation-free, widely accessible alternative to functional lung imaging in managing pulmonary vascular diseases.Clinical trial numberNot applicable.

EPAS-1 as a potential D-dimer alternative in pulmonary embolism evaluation

Abstract Background and Objectives We aimed in this study was to determine the changes in EPAS-1 levels, which is a biomarker proven to increase with hypoxia, at the time of diagnosis and after treatment in addition to the laboratory parameters and scoring systems examined at the time of admission in patients with pulmonary thromboembolism. Methods Our study included 60 pulmonary embolism patients followed in the Cardiology clinic and 60 control groups with similar demographic characteristics. Laboratory parameters determined at the time of admission were examined. Pulmonary embolism risk and severity scores were applied and EPAS-1 levels were also studied. To determine the response, EPAS-1 levels were checked 3 days later and compared with the control group. Results There was no difference between the two groups in terms of demographic characteristics and comorbidities.EPAS-1 levels were found to be higher at the time of diagnosis compared to the control group ((3.6±1.42/1.57±0.45), p&amp;lt;0.001). It showed a statistically significant positive correlation with PESI severity score and risk score in the patient group. EPAS-1 levels were shown to decline with the treatment of the patients and the tendency to decline was different according to the types of treatment. In patients who died, EPAS-1 levels continued to increase despite treatment (p:0.014). Conclusions Our study is important in that EPAS-1 levels, which are correlated with scoring systems and other laboratory parameters used in pulmonary embolism patients, can be used as a predictive value in the diagnostic process of the disease and play a complementary role in the evaluation of treatment response.

Patient engagement in pulmonary embolism research: Insights form the Attend-PE study

Abstract Background There is growing recognition of the significance of a close collaboration between patients, clinicians, and researchers to ensure that research and health service delivery effectively meets the needs of end users [1-3]. However, there is limited understanding of best practices for patient engagement in research among patients with venous thromboembolism, and there is sparse knowledge about challenges to and facilitators of this process [4, 5]. Purpose To describe and explore the process and evaluate the impact of patient engagement in the development of a structured nurse-led post pulmonary embolism care model (the Attend-PE model). Method This prospective embedded case study of patient engagement was conducted within the research project - A structured Integrated post Pulmonary Embolism care model (Attend-PE). The study was based on documents from patient journey mapping (PJM), documents and field notes from workshops, and semi-structured interviews with two patients with pulmonary embolism, two clinicians working with pulmonary embolism patients and the Attend-PE researchers. Data were analyzed based on research questions guided by the United Kingdom six Standards for Public Involvement; Inclusive opportunities, Working together, Support &amp; learning, Governance, Communications and Impact [6]. Result Patients played a crucial role throughout the entire Attend-PE study, contributing to research questions, design, execution, and dissemination, as illustrated in Figure 1. The patients were involved at a higher engagement level in the co-creation of the Attend-PE model and co-creation of patient education and information material. Comparatively the engagement level was lower in decisions regarding outcomes, feasibility testing and implementation of the Attend-PE model, as shown in Figure 2. Notably, despite lower engagement level, the continuous involvement in the research process was invaluable to the patients. This ensured that they maintained insight in the research process, even though their contributions varied in the different phases. Important facilitators of patient engagement within the Attend-PE were related to "Inclusive opportunities" and "Support and learning". Patients highlighted the importance of being a part of the process, working together as a team, and being prepared for the work. Important challenges to patient involvement related to "Communication" and "Governance", including lack of expectation alignment and communication regarding clinical elements where clinicians often dominated the discussions. Conclusion Patient involvement has been invaluable in the development of a structured nurse-led post pulmonary embolism care model. Further, patients will be involved in evaluation of the national implementation process and dissemination of study results.Figure 1Figure 2

Ultrasound assisted, catheter-directed thrombolysis for acute intermediate-high and high risk pulmonary embolism: focus on safety for oncological patients

Abstract Background Catheter-based revascularization procedures have been developed as an alternative to systemic thrombolysis or surgical embolectomy for intermediate-high and high risk pulmonary embolism (PE) patients with. Little is known about the outcomes of oncological patients, who are notably at higher bleeding risk, undergoing such procedure. Purpose The USAT IH-PE registry is a retrospective and prospective multicenter registry of patients treated with ultrasound-facilitated, catheter-directed thrombolysis. We sought to determine whether patients with active cancer experience more bleeding complications and need for transfusions. Methods: Between March 2018 and July 2023, 102 patients were included. The majority were at intermediate–high-risk PE (86%), mostly female (57%), with a mean age of 63.7 ± 14.5 years. Most patients (77.8%) had a bilateral involvement of the main pulmonary arteries on CT scan and 9 patients (8.8%) had at least one prior episode of PE. 28.4% had active cancer. We compared the oncological and non-oncological subpopulations. The primary endpoints were bleeding complications (defined as BARC &amp;gt; IIIa) and need for transfusion. Results Overall, 12% of patients experienced bleeding complications, of which 4.9% were BARC ≥ 3. When comparing bleeding complications, defined as BARC &amp;gt; IIIa or the need for transfusion, no significant difference was found between patients with active cancer and those without (OR 0.61, 95% CI 0.01-6.62, p=1, and OR 2.43, 95% CI 0.61-9.48, p=0.18, respectively). Conclusions In the USAT IH-PE registry, where a significant proportion of patients have active cancer, no significant difference in bleeding complications was observed in these subjects. This finding confirms the safety of the procedure, even in a subpopulation traditionally considered at higher risk for bleeding.

A simple and reliable computed tomographic measure for the evaluation of right ventricle remodelling in acute PE: right ventricle apical angle

Abstract Background and aims In patients with acute pulmonary embolism (PE), right ventricular (RV) dysfunction as assessed by computed tomography (CT) and /or echocardiography has been considered to predict in-hospital and 30-day outcomes. In this study we proposed a novel CT measure for RV function, the apical angle (α1) between the RV free wall and the interventricular septum (IVS), and for the left ventricle (LV) function, the apical angle (α2) between the LV free wall and the IVS. We aimed to evaluate the predictive value of these angles to determine clinical and hemodynamic severity and in-hospital mortality (IHM) in acute PE patients. Methods The study population comprised retrospectively evaluated 536 patients (age 59+-16.2 years, female 55.3 %) with acute PE in whom diagnostic work-up and risk-based treatments have been performed in accordance with currently available acute PE Guidelines. The severity of pulmonary arterial (PA) obstruction (Qanadli score) and RV/LV ratio were assessed on CT, and RV function and non-invasive estimation of pulmonary arterial systolic pressures (PASP) were evaluted with echocardiography. The α1 was defined as the angle between the line from tricuspid medial annulus to the RV apex and second line from tricuspid lateral annulus to the RV apex, whereas α2 was defined as the angle between the line from mitral medial annulus to the LV apex and second line from mitral lateral annulus to the LV apex. Results Anticoagulant treatment only and intravenous tissue plasminogen activator were noted in 49.6 % and 17.9 % of patients, respectively. Ultrasound-assisted thrombolysis and rheolytic thrombectomy were also used in 25% and 7.5 % of patients, respectively. The IHM rate was 5.9 %. The increase in α1 was associated with a decrease in TAPSE/PASP ratio, and an increase in PESI score and a higher risk status (p=0.047, p&amp;lt;0.001, p=0.001 respectively), but α2 showed no relation to PE severity (p=0.78). The value of α1 in predicting in-hospital mortality was evaluated with a logistic regression analysis with a model including PESI score, RV/LV ratio and α1. PESI score and α1 significantly predicted IHM (p= &amp;lt;0.001 and 0.027, respectively. OR for a1 1.15, CI 95%[1.06-1.27]), but RV/LV ratio did not. In the receiver operating curve (ROC) analysis for IHM prediction, the cut-off value of 1.168 for α1/α2 ratio [area under the curve (AUC): 0.721; sensitivity:76.92 % and specificity: 65.8 %] and the cut-off value of 32.47 for α1 ( AUC: 0.718 ; sensitivity: 84.67 % and specificity: 59.5 %) provided higher prediction compared with cut-off value of 1.29 for RV/LV ratio ( AUC : 0.604 ; sensitivity 76.9 % and specificity 45.87 %). Conclusion Either α1 or α1/α2 ratio evaluation on CT seems to represent a simple and reliable approach in the assessment of RV acute remodelling in response to thrombo-obstructive pressure burden and for prediction of outcome in patients with acute PE.Alpha 1 angle of different risk groupsROC curve

Elective endovascular reperfusion therapies in intermediate-high risk pulmonary embolism after PERT assesment

Abstract Background The ideal management of patients with intermediate-high risk (IHR) pulmonary embolism (PE) is still unknown. A multidisciplinary approach by Pulmonary Embolism Response Teams (PERT) in combination with the advent of endovascular therapies sounds promising. Purpose Evaluate in-hospital events of elective endovascular reperfussion therapies in selected IHR PE patients after PERT assesment in a single center initial experience. Methods Analysis of consecutive patients with PE admitted from Jan/2017 to Jan/2024. The in-hospital evolution of an elective invasive strategy defined by an institutional PERT (since April/2021) in IHR PE patients was compared against the current standard of care (isolated anticoagulation and reperfusion only after hemodynamic collapse). Patients with limitations of therapeutic efforts due to comorbidities were excluded. Results 361 patients with PE were treated with 76 (21.1%) stratified as IHR. After excluding 14 patients due to limitations of therapeutic efforts (78±9.4 years; 64.3% active cancer), 62 were included for analysis. An elective endovascular treatment was performed in 20 (31.3%) patients; these were younger and with fewer comorbidities. However, they had more tachypnea, greater central distribution of thrombotic burden and signs of right ventricle overload assessed by flattening of the interventricular septum. Baseline characteristics, clinical presentation and management are described in table 1. Within the invasive group, endovascular reperfusion was performed with local thrombolysis (70%), aspiration thrombectomy (15%) or their combination (15%). During hemodynamic evaluation, hidden shock was detected in 42.9% (6/14), with improvements in cardiac index observed after reperfusion therapy (n=8; 2.1 vs. 2.5). Improvement was also observed in pulmonary artery systolic pressure (n=14, 56.9 vs. 37.1mmHg; p&amp;lt;0.001) and right ventricular function (n=15, TAPSE 16 vs. 22mm; p&amp;lt;0.001). Compared with the current standard of care, an elective invasive approach was associated with a shorter hospital stay (6.5 vs. 9 days; p=0.02), less hemodynamic collapse (0% vs. 19.1%; p=0.04), need for mechanical ventilation (0% vs. 19.1%; p=0.04) and in-hospital mortality (0% vs. 21.4%; p=0.04) without differences in the incidence of major bleeding (Fig 1). After multivariate logistic regression analysis, the mortality benefit persisted in favor of an invasive strategy (p=0.014). Conclusions An "elective" invasive strategy in selected patients with IHR PE after PERT assessment was safe and resulted in less major in-hospital cardiovascular events in a single-center initial experience. Although these results should be taken with caution given the limitations of this study (single-center, small observational sample), they are in line with recent reports and are the focus of ongoing large randomized clinical trials.Table 1

Routine use of ultrasound-assisted catheter-directed thrombolysis for the management of intermediate-high risk pulmonary embolism: a service evaluation project

Abstract Background Intermediate-high risk Pulmonary Embolism (PE) has considerable morbidity. Conservative management could be sub-optimal. Ultrasound-Assisted Catheter-Directed Thrombolysis (UACDT) is used in our centre for the routine management of this presentation. Purpose We assessed the procedure safety and short-term outcomes by reviewing locally performed procedures. Methods This is an observational retrospective cohort study, with a historic control group. Our centre is a District General Hospital (DGH) in the United Kingdom, and we receive referrals from local acute hospitals. Since the introduction of this service in June 2018 until November 2023, 129 patients (2 patients/month) received routine management with UACDT for intermediate-high risk PE. The controls are 75 acute PE patients of comparable risk classes, managed from January to December 2016. We assessed procedural and in-hospital outcomes including minor, major bleeding/complications and death. We also assessed Length of Stay (LoS) in hospital, recurrent Venous Thrombo-Embolism (VTE) and re-admission rates for recurrent PE at 30 days. Reduction of oxygen requirements and improved estimated systolic Pulmonary Artery Pressure (sPAP) post-procedure were assessed as surrogate measures. Continuous variables were analysed with a Mann-Whitney U test, and categorical variables with a Chi-square Test. Results Baseline demographics are listed in Table 1. Mean duration between CT Pulmonary Angiography (CTPA) and the UACDT procedure was 1.6 (±SD 1.4) days, including inter-hospital transfer. Only 6% (8/129) of UACDT cohort received ≤12 mg standard alteplase dose. In the control group, 4% (3/75) of patients received standard 100mg systemic thrombolysis. There was no significant difference in the rates of minor (p= 0.9), major bleeding/complications (p= 0.8), or death (p= 1.0) between both groups. There was also no significant difference in rates of recurrent VTE (p= 1.0) or re-admission within 30 days for PE (p=0.1) (Table 2). LoS in hospital data were ratified, to exclude inappropriate delays (e.g. physiotherapy requirements, etc). We used the date when the patient was declared medically fit for discharge, and no significant difference was noted (p= 0.2). This was confirmed with a regression analysis of UACDT treatment effect (p= 0.9, CI= -3.5 to 3.1). Nonetheless, there was a 25% reduction of median LoS in hospital from 8 days in the controls to 6 days with UACDT. The proportion of patients requiring O2 was also reduced from 69% (89/129) to 41% (54/129) on day 1 post-procedure. A significant reduction of the estimated sPAP by TTE post-procedure was detected by a mean of 10.4 (±SD 13.9) mmHg (p= &amp;lt;0.01). Conclusion UACDT is generally safe with low complications rate. Compared to the control group, there was a reduction in absolute deaths and median LoS in hospital. This can be secondary to the significant acute reduction of systolic pulmonary artery pressure identified.

Pulmonary artery pulsatility index evaluation in intermediate-to-high and high-risk pulmonary embolism patients underwent transcatheter intervention

Abstract Background The clinical impact of pulmonary embolism (PE) transcatheter intervention on the right ventricular function and its potential role as procedural outcomes has to be defined. Methods Consecutive patients who underwent pulmonary transcatheter intervention between 2021 and 2023 were included in an observational fashion. Data about clinical characteristics, PE risk stratification, pre and post-interventional pulmonary artery pressure (PAP) and Pulmonary Artery Pulsatility Index (PAPi) were collected. The primary endpoint was a composite of in-hospital death or repeated intervention. Results 49 patients were included, mostly female gender (61.2%), with a mean age of 67±12,9 years old, 79.6% with &amp;gt; 1 PE risk factor, and 55% of them stratified as high-risk (HR) PE. 34.6% of the patients were treated with transcatheter thrombolysis (all in the intermediate-to-high-risk cohort), 20% with FlowTriever device, 53.4% with Indigo Cath8 or Lightning 12 device, 8.1% of the procedure was performed under ECMO support. All patients classified in intermediate-to-high risk (IHR) survived, and the mean PAP was reduced (33.4±10.9 to 24.3±7.1 mmHg p&amp;lt;0.01), as well as PAPi (2,3±0.35 to 1.68±0.26 p&amp;lt;0.01). 22% of the patients In IHR experienced the primary endpoint, in these populations, the mean PAP (pre 33±4.1 vs post 30.5±4.6 p=0.58) and PAPi (pre 1.35±.0.6 vs post 1.4±0.6 p=0.39) did not change significantly. On the other side, those who survived without events had a slight significative reduction in mean PAP (pre 32±6.7 vs post 24.6±4.3 p&amp;lt;0.02) while the PAPi significantly increased (1.2±0.6 vs 1.8±0.2 p&amp;lt;0.01). In the HR population, a delta PAPi &amp;gt; 0.45 demonstrated a 65.7% sensitivity and 75% Specificity for the primary outcome AUC 0.83 at ROC curve analysis. Conclusion Pulmonary Thrombus aspiration significantly changes the PAP and PAPi in patients with acute PE. While in IHR patients the overperforming PAPi seems to normalize, in HR patients it increases and may be a marker of procedural success and right ventricle recovery.

Right ventricular-pulmonary artery coupling for prognostication in acute pulmonary embolism.

Acute pulmonary embolism (PE) increases pulmonary pressure and impair right ventricular (RV) function. Echocardiographic investigation can quantify this mismatch as the tricuspid annular plane systolic excursion (TAPSE) to pulmonary arterial systolic pressure (PASP) ratio. The aim of the study was to investigate the prognostic capabilities of TAPSE/PASP ratio in patients with acute PE. We utilized the RIETE registry to analyze consecutive hemodynamically stable PE patients. We used multivariable logistic regression analyses to assess the association between the TAPSE/PASP ratio and 30-day all-cause mortality across the strata of European Society of Cardiology (ESC) risk categories. We included 4,478 patients, of whom 1,326 (30%) had low-risk, 2,425 (54%) intermediate-low risk, and 727 (16%) intermediate-high risk PE. Thirty-day mortality rates were 0.7%, 2.3% and 3.4%, respectively. Mean TAPSE/PASP ratio was 0.65±0.29 in low-risk patients, 0.46±0.30 in intermediate-low risk, and 0.33±0.19 in intermediate-high risk patients. In multivariable analyses, there was an inverse association between TAPSE/PASP ratio and 30-day mortality (adjusted OR 1.32 [95%CI 1.14-1.52] per 0.1 decrease in TAPSE/PASP). TAPSE/PASP ratio below optimal cut-points was associated with increased mortality in low- (<0.40, aOR: 5.88; 95%CI:1.63-21.2), intermediate-low (<0.43, aOR: 2.96; 95%CI:1.54-5.71) and intermediate-high risk patients (<0.34, aOR: 4.37; 95%CI:1.27-15.0). TAPSE/PASP <0.44 showed net reclassification improvement of 18.2% (95%CI:0.61-35.8) vs. RV/LV ratio >1, and 27.7% (95%CI:10.2-45.1) vs. ESC risk strata. Decreased TAPSE/PASP ratio was associated with increased mortality. The ratio may aid in clinical decision-making, particularly for intermediate-risk patients for whom the discriminatory capability of the current risk stratification tools is limited.