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Introduction: Chronic thromboembolic pulmonary hypertension (CTEPH) is often diagnosed late in acute pulmonary embolism survivors: more efficient testing to expedite diagnosis may considerably improve patient outcomes. The InShape II algorithm safely rules out CTEPH (failure rate 0.29%) while requiring echocardiography in only 19% of patients but may be improved by adding detailed reading of the computed tomography pulmonary angiography diagnosing the index pulmonary embolism., Methods: We evaluated 12 new algorithms, incorporating the CTEPH prediction score, ECG reading, N‑terminal pro-brain natriuretic peptide levels and dedicated computed tomography pulmonary angiography reading, in the international InShape II cohort (n=341) and part of the German FOCUS cohort (n=171). Evaluation criteria included failure rate, defined as the incidence of confirmed CTEPH in pulmonary embolism patients in whom echocardiography was deemed unnecessary by the algorithm, and the overall net reclassification index compared to the InShape II algorithm., Results: The algorithm starting with computed tomography pulmonary angiography reading of the index pulmonary embolism for six signs of CTEPH, followed by ECG/N-terminal pro-brain natriuretic peptide level assessment and echocardiography resulted in the most beneficial change compared to InShape II, with a need for echocardiography in 20% (+5%), a failure rate of 0% and a net reclassification index of +3.5%, reflecting improved performance over the InShape II algorithm. In the FOCUS cohort, this approach lowered echocardiography need to 24% (-6%) and missed no CTEPH cases, with a net reclassification index of +6.0%., Conclusion: Dedicated computed tomography pulmonary angiography reading of the index pulmonary embolism improved the performance of the InShape II algorithm and may improve the selection of pulmonary embolism survivors who require echocardiography to rule out CTEPH., Competing Interests: Conflict of interest: S. Barco received research support from Boston Scientific, Medtronic, Concept Medical, Sanofi and Novartis, all outside this manuscript. M. Delcroix received consulting fees from Actelion/Janssen/J&J, Acceleron/MSD, Gossamer and Ferrer; and payment or honoraria for lectures, presentations, manuscript writing or educational events from Actelion/Janssen/J&J, Acceleron/MSD and Ferrer, all outside the submitted work. L. Jara-Palomares reports grants from Daichii, Rovi, GlaxoSmithKline, BMS, Leo Pharma, MSD and Johnson and Johnson. H. Vliegen received grants from Johnson and Johnson; payment or honoraria for lectures, presentations, manuscript writing or educational events from Novartis and Boehringer Ingelheim; and participates on a data safety monitoring board or advisory board for Amarin and Daiichi Sankyo. S.V. Konstantinides reports grants or contacts from Daiichi Sankyo; consulting fees from Boston Scientific, Inari Medical, Bayer AG, Penumbra Inc. and Daiichi Sankyo; and payment or honoraria for lectures, presentations, manuscript writing or educational events from Boston Scientific and Penumbra Inc., all outside of the submitted work. F.A. Klok received research support from Bayer, BMS, BSCI, AstraZeneca, MSD, Leo Pharma, Actelion, Farm-X, The Netherlands Organisation for Health Research and Development, The Dutch Thrombosis Foundation, The Dutch Heart Foundation and the Horizon Europe Program, all outside this manuscript. The remaining authors declare no competing interests., (Copyright ©The authors 2024. For reproduction rights and permissions contact permissions@ersnet.org.)

Background: Right ventricle (RV) dysfunction increases the risk of death from pulmonary embolism (PE). C-reactive protein (CRP) might identify RV inflammation and dysfunction in patients with PE., Methods: This cohort study enrolled consecutive stable patients with acute PE between 2017 and 2023. We stratified patients by quartiles of CRP. We evaluated the association between CRP quartiles and the presence of RV dysfunction, and used multivariable models to assess for an association between CRP and the outcomes of all-cause and PE-specific mortality during the 30 days of follow-up after PE diagnosis., Results: The study included 633 stable patients with PE. Patients without RV dysfunction had significantly lower median (IQR) CRP levels compared with patients with RV dysfunction (n=509, 31.7 [10.0-76.4]mg/L vs n=124, 45.4 [16.0-111.4]mg/L; P=0.018). CRP showed a statistically significant positive association with the presence of RV dysfunction (P<0.01). On multivariable analysis, CRP level was not significantly associated with 30-day all-cause mortality (adjusted odds ratio [OR] per mg/L increment, 1.00; 95% CI, 1.00-1.01; P=0.095), but higher CRP was associated with significantly higher PE-related mortality (adjusted OR, 1.01; 95% CI, 1.00-1.01; P=0.026). Compared with patients in CRP quartile 1, patients in quartiles 2, 3, and 4 had a stepwise increase in the adjusted odds of 30-day all-cause death of 2.41 (P=0.148), 3.04 (P=0.062), and 3.15 (P=0.052), respectively., Conclusions: As an indicator of RV dysfunction, CRP may improve risk stratification algorithms for hemodynamically stable patients with acute symptomatic PE., (Copyright © 2024 SEPAR. Published by Elsevier España, S.L.U. All rights reserved.)

Background: The effect of supplemental oxygen therapy in patients with intermediate-risk pulmonary embolism (PE) who do not have hypoxemia at baseline is uncertain., Research Question: Does supplemental oxygen improve echocardiographic parameters in nonhypoxemic patients with intermediate-risk PE?, Study Design and Methods: This pilot trial randomly assigned nonhypoxemic patients with stable PE and echocardiographic right ventricle (RV) enlargement to receive anticoagulation plus supplemental oxygen for the first 48 h vs anticoagulation alone. The primary outcome was normal echocardiographic RV size 48 h after randomization. Secondary efficacy outcomes were the numerical change in the RV to left ventricle (LV) diameter ratio measured 48 h and 7 days after randomization with respect to the baseline ratio measured at inclusion., Results: The study was stopped prematurely because of the COVID-19 pandemic after recruiting 70 patients (mean ± SD age, 67.3 ± 16.1 years; 36 female [51.4%]) with primary outcome data. Forty-eight h after randomization, normalization of the RV size occurred in 14 of the 33 patients (42.4%) assigned to oxygen and in eight of the 37 patients (21.6%) assigned to ambient air (P = .08). In the oxygen group, the mean RV to LV ratio was reduced from 1.28 ± 0.28 at baseline to 1.01 ± 0.16 at 48 h (P < .001); in the ambient air group, mean RV to LV ratios were 1.21 ± 0.18 at baseline and 1.08 ± 0.19 at 48 h (P < .01). At 90 days, one major bleeding event and one death (both in the ambient air group) had occurred., Interpretation: In analyses limited by a small number of enrollees, compared with ambient air, supplemental oxygen did not significantly increase the proportion of patients with nonhypoxemic intermediate-risk PE whose RV to LV ratio normalized after 48 h of treatment. This pilot trial showed improvement in some ancillary efficacy outcomes and provides support for a definitive clinical outcomes trial., Trial Registry: ClinicalTrials.gov; No.: NCT04003116; URL: www., Clinicaltrials: gov., Competing Interests: Financial/Nonfinancial Disclosures The authors have reported to CHEST the following: L. J.-P. reports personal fees from Bayer Hispania, Actelion, Rovi, Pfizer, Menarini, and Leo Pharma, outside the submitted work. R. O.-C. has served as an advisor or consultant for Leo Pharma, Actelion, Bayer Hispania, and Sanofi; as a speaker or a member of a speakers’ bureau for Leo Pharma, Sanofi, and Rovi; and has received grants for clinical research from Leo Pharma and Bayer Hispania. P. R.-A. has served as an advisor or consultant for Leo Pharma, Pfizer, and Viatris; has served as a speaker or a member of a speakers’ bureau for Bristol-Myers Squibb, Daiichi Sankyo, Leo Pharma, ROVI, and Viatris; and has received grants for clinical research from ROVI. M. M. has served as an advisor or consultant for Leo Pharma and Sanofi; has served as a speaker or a member of a speakers’ bureau for Bristol-Myers Squibb and Sanofi; and has received grants for clinical research from Sanofi and ROVI. B. B. reports that he is a consulting expert, on behalf of the plaintiff, for litigation related to two specific brand models of inferior vena cava filters. D. J. has served as an advisor or consultant for Bayer HealthCare Pharmaceuticals, Bristol-Myers Squibb, Daiichi Sankyo, Leo Pharma, Pfizer, ROVI, and Sanofi; has served as a speaker or a member of a speakers’ bureau for Bayer HealthCare Pharmaceuticals, Bristol-Myers Squibb, Daiichi Sankyo, Leo Pharma, ROVI, and Sanofi; and has received grants for clinical research from Daiichi Sankyo, Sanofi, and ROVI. None declared (D. B., D. D., C. R., J. M., A. R., J. L. L., R. L., L. C., A. M.)., (Copyright © 2023 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: Chronic thromboembolic pulmonary hypertension (CTEPH) is the most severe long-term complication of acute pulmonary embolism (PE). We aimed to evaluate the impact of a symptom screening programme to detect CTEPH in PE survivors., Methods: This was a multicentre cohort study of patients diagnosed with acute symptomatic PE between January 2017 and December 2018 in 16 centres in Spain. Patients were contacted by phone 2 years after the index PE diagnosis. Those with dyspnoea corresponding to a New York Heart Association (NYHA)/WHO scale≥II, visited the outpatient clinic for echocardiography and further diagnostic tests including right heart catheterisation (RHC). The primary outcome was the new diagnosis of CTEPH confirmed by RHC., Results: Out of 1077 patients with acute PE, 646 were included in the symptom screening. At 2 years, 21.8% (n=141) reported dyspnoea NYHA/WHO scale≥II. Before symptom screening protocol, five patients were diagnosed with CTEPH following routine care. In patients with NYHA/WHO scale≥II, after symptom screening protocol, the echocardiographic probability of pulmonary hypertension (PH) was low, intermediate and high in 76.6% (n=95), 21.8% (n=27) and 1.6% (n=2), respectively. After performing additional diagnostic test in the latter 2 groups, 12 additional CTEPH cases were confirmed., Conclusions: The implementation of this simple strategy based on symptom evaluation by phone diagnosed more than doubled the number of CTEPH cases. Dedicated follow-up algorithms for PE survivors help diagnosing CTEPH earlier., Trial Registration Number: NCT03953560., Competing Interests: Competing interests: SM-R was supported by two research grants from the Neumosur Association and SEPAR National Association. CG-C reports payment or honoraria from LEO Pharma. JMPN reports payment or honoraria from Bayer, ROVI and LEO Pharma; and support for attending meetings and/or travel from ROVI. ML reports support for attending meetings and/or travel from MSD. MAA-A reports grants or contracts from Pfizer, Alnylam and Akcea-Ionis; and participation on a Data Safety Monitoring Board or Advisory Board for Pfizer, Bayer and Alnylam. JC-G reports payment or honoraria from Sanofi, ROVI, Bristol, Aspen and Pfizer; and support for attending meetings and/or travel from Sanofi and ROVI. JAP-L reports payment or honoraria from ROVI; and support for attending meetings and/or travel from Pfizer. LJ-P obtained funding for this study from MSD. Grant outside this work and paid to Neumosur Foundation, received payment for lectures and presentations from Actelion Pharmaceuticals, Bayer HealthCare Pharmaceuticals, MSD, Leo Pharma, Pfizer, ROVI, Bristol-Myers Squibb. FAK has received research support from Bayer, Bristol-Myers Squibb, Actelion, Boston Scientific, Leo Pharma, PharmX, The Netherlands Organisation for Health Research and Development, The Dutch Thrombosis Association, The Dutch Heart Foundation and the Horizon Europe program, all outside this work and paid to his institution. The remaining authors (AB-Q, PJM-Y, PL-M, IF-A, JBL-S, MP-P, CB-M, AR-M, MP-S, THE, RO, AM and MB-H) declare no conflict of interest., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Pulmonary embolism (PE) is a prevalent condition with a substantial morbi-mortality worldwide. Proper risk stratification of PE is essential for identifying the most suitable therapeutic strategy and the optimal care setting for the patient. This process entails evaluating various factors, including symptoms, comorbidities, and right heart dysfunction., Areas Covered: This review assesses the tools and methods utilized to identify and stratify individuals based on the probability of developing deterioration or death related to PE. Current guidelines divide PE into three groups: high-risk (previously termed massive) PE, intermediate-risk (sub-massive) PE, and low-risk PE. Various risk scores, such as the simplified pulmonary embolism severity index (sPESI), Bova score, and the FAST score (incorporating Heart-Fatty Acid binding protein [H-ABP], Syncope, Tachycardia), aid in identifying patients at higher risk. Additionally, the Hestia score is instrumental in pinpointing low-risk patients., Expert Opinion: Presently, there is a dearth of high-quality frameworks for the optimal management and treatment of PE patients at risk of hemodynamic collapse. A consortium of experts is in the process of formulating a new conceptual model for risk stratification, taking into account a comprehensive array of variables and outcomes to facilitate more individualized management of acute PE.

COVID-19 is associated with endothelial activation in the setting of a potent inflammatory reaction and a hypercoagulable state. The end result of this thromboinflammatory state is an excess in thrombotic events, in particular venous thromboembolism. Pulmonary embolism (PE) has been of special interest in patients with COVID-19 given its association with respiratory deterioration, increased risk of intensive care unit admission, and prolonged hospital stay. The pathophysiology and clinical characteristics of COVID-19-associated PE may differ from the conventional non-COVID-19-associated PE. In addition to embolic events from deep vein thrombi, in situ pulmonary thrombosis, particularly in smaller vascular beds, may be relevant in patients with COVID-19. Appropriate prevention of thrombotic events in COVID-19 has therefore become of critical interest. Several changes in viral biology, vaccination, and treatment management during the pandemic may have resulted in changes in incidence trends. This review provides an overview of the pathophysiology, epidemiology, clinical characteristics, and risk factors of COVID-19-associated PE. Furthermore, we briefly summarize the results from randomized controlled trials of preventive antithrombotic therapies in COVID-19, focusing on their findings related to PE. We discuss the acute treatment of COVID-19-associated PE, which is substantially similar to the management of conventional non-COVID-19 PE. Ultimately, we comment on the current knowledge gaps in the evidence and the future directions in the treatment and follow-up of COVID-19-associated PE, including long-term management, and its possible association with long-COVID., Competing Interests: L.O-P: Nothing to disclose.A.H.T.: Nothing to disclose.P.S.: Nothing to disclose.T.S.P.: Nothing to disclose.H.D.A.: Outside the submitted work, H.A.D. is a consultant for Silk Road Medical for Philips.L.J-P.: Grants from Leo Pharma and MSD and personal fees from Daichii, Rovi, GlaxoSmithKline, and Actellion outside the submitted work.M.S.: Co-principal investigator of the RAPID trial.D.J.A.: Consulting fees or honoraria from Abbott, Amgen, AstraZeneca, Bayer, Biosensors, Boehringer Ingelheim, Bristol-Myers Squibb, Chiesi, Daiichi-Sankyo, Eli Lilly, Haemonetics, Janssen, Merck, PhaseBio, PLx Pharma, Pfizer, and Sanofi. D.J.A. also declares that his institution has received research grants from Amgen, AstraZeneca, Bayer, Biosensors, CeloNova, CSL Behring, Daiichi-Sankyo, Eisai, Eli Lilly, Gilead, Idorsia, Janssen, Matsutani Chemical Industry Co., Merck, Novartis, Osprey Medical, Renal Guard Solutions, and the Scott R. MacKenzie Foundation.G.Y.H.L.: Consultant and speaker for BMS/Pfizer, Boehringer Ingelheim, and Daiichi-Sankyo. No fees are received personally.B.B.: Reports that he is a consulting expert, on behalf of the plaintiff, for litigation related to two specific brand models of IVC filters., (Thieme. All rights reserved.)

Introduction: Chronic thromboembolic pulmonary hypertension (CTEPH) is a long-term sequel to pulmonary embolism (PE) whose incidence varies according to different published studies. We have carried out this study to determine its incidence within 2 years after index pulmonary embolism and to study limitations to an early diagnosis., Material and Methods: OSIRIS is a multicentre, longitudinal cohort study. Patients were followed for 3, 6, 12, and 24 months after pulmonary embolism using a structured three-step algorithm. A physician-centered questionnaire at least one positive response in a screening proceeded to the second step, transthoracic echocardiography. The third step consisted of ventilation/perfusion lung scintigraphy and right heart catheterisation. A transthoracic echocardiography was performed in patients without positive response in the screening questionnaire after 2 years. CTEPH diagnosis required haemodynamic confirmation by right heart catheterisation and mismatched perfusion defects on lung scintigraphy., Results: A total of 1191 patients were enrolled in 18 Spanish hospitals. Cumulative CTEPH incidence after 2-years PE was: 2.49 % (95 % CI: 1.68-3.56) and the incidence rate of CTEPH was 1.1 cases per 1000 person-months (95 % CI: 0.725; 1.60). The CTEPH algorithm presented a lack of adherence of 29 %; patient and physician preferences posed barriers to the triage algorithm The screening questionnaire, in patients who completed the follow-up, shows a specificity of 91.3 % (89.0-93.2 %) and negative predictive value of 99.4 % (98.4-99.8 %).., Conclusions: OSIRIS provides practiced clinical based data on the chronic thromboembolic pulmonary hypertension incidence and identified barriers to the implementation of a 3-step triage algorithm for its detection., Clinical Trial Registration: clinicaltrials.gov identifier: NCT03134898., Competing Interests: Declaration of competing interest Authors declared to have no conflicts., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: In patients with intermediate-risk pulmonary embolism (PE), reversal of hypoxic vasoconstriction could constitute a target for treatment that protects the right ventricular (RV) function until endogenous fibrinolysis occurs. The Air vs oxygen for Intermediate-Risk pulmonary embolism (AIR) trial aims to assess the effect of oxygen therapy in patients with intermediate-risk acute PE who do not have hypoxemia at baseline., Methods and Analyses: AIR is a prospective, multicenter, randomized, open-label, parallel-group, proof-of-concept trial. A total of 90 patients hospitalized with intermediate-risk PE and an oxygen saturation of 90% or higher at baseline will be randomized in a 1:1 fashion to receive supplemental oxygen or ambient air. The primary outcome is a RV/LV diameter ratio equal or less than 1.0 on echocardiography measured 48 hours after the start of treatment. Secondary efficacy outcomes are the numerical change in the ratio of the RV to the LV diameter measured 48 hours and 7 days after the start of treatment, with respect to the baseline ratio measured at randomization. Clinical adverse events will be also collected., Results: Enrollment started in July 2019 and is expected to proceed until 2022. Median age of the first 50 patients was 74 years (interquartile range, 61-81), and 50% were female., Conclusions: This multicenter trial will provide information about the value of supplemental oxygen in patients with intermediate-risk acute PE who do not have hypoxemia at baseline. The results will contribute to research that may assist patients with intermediate-risk PE in the future., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Introduction: Syncope has been shown to be a risk factor of bleeding in patients receiving thrombolytic therapy for acute pulmonary embolism (PE). Whether syncope predicts bleeding in a broader population of patients with PE remains unknown., Methods: We used the RIETE registry data to assess whether initial presentation with syncope could predict bleeding in PE patients receiving anticoagulant therapy, and to explore the association between presence of syncope and timing and site of major bleeding events., Results: Among 45,765 patients with acute PE from March 2001 to January 2021, 6760 (14.8%) had syncope. Patients with syncope were older and more likely to have hypotension, tachycardia, hypoxaemia or elevated troponin levels than those without syncope. They also were more likely to receive thrombolytics. During the first 90 days, 1097 patients (2.4%) suffered major bleeding (gastrointestinal 335, hematoma 271 and intracranial 163) and 3611 died (158 had fatal bleeding). Patients with syncope had a higher rate of major bleeding (odds ratio [OR]: 1.63; 95% CI: 1.41-1.89) and a nonsignificantly higher rate of fatal bleeding (OR: 1.47; 95% CI: 0.99-2.17) than those without syncope. Multivariable analysis confirmed that patients with syncope were at increased risk for major bleeding (adjusted hazard ratio [aHR]: 1.34; 95% CI: 1.15-1.55). On sensitivity analysis, the increased risk for major bleeding was confirmed in patients initially receiving anticoagulant therapy without thrombolytics at 7 days (aHR: 1.47; 95% CI: 1.13-1.91) and 90 days (aHR: 1.33; 95%CI: 1.13-1.56)., Discussion: Syncope is a predictor of major bleeding events in patients with PE, even among those receiving anticoagulation monotherapy., (© 2022 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd.)

Background: The length of hospital stay (LOS) for acute pulmonary embolism (PE) varies considerably. Whether the upfront use of a PE prognostic assessment and management pathway is effective in reducing the LOS remains unknown., Methods: We conducted a randomised controlled trial of adults hospitalised for acute PE: patients were assigned either to a prognostic assessment and management pathway involving risk stratification followed by predefined criteria for mobilisation and discharge (intervention group) or to usual care (control group). The primary end-point was LOS. The secondary end-points were the cost of prognostic tests and of hospitalisation, and 30-day clinical outcomes., Results: Of 500 patients who underwent randomisation, 498 were included in the modified intention-to-treat analysis. The median LOS was 4.0 days (interquartile range (IQR) 3.7-4.2 days) in the intervention group and 6.1 days (IQR 5.7-6.5 days) in the control group (p<0.001). The mean total cost of prognostic tests was EUR 174.76 in the intervention group, compared with EUR 233.12 in the control group (mean difference EUR -58.37, 95% CI EUR -84.34- to -32.40). The mean total hospitalisation cost per patient was EUR 2085.66 in the intervention group, compared with EUR 3232.97 in the control group (mean difference EUR -1147.31, 95% CI EUR -1414.97- to -879.65). No significant differences were observed in 30-day readmission (4.0% versus 4.8%), all-cause mortality (2.4% versus 2.0%) or PE-related mortality (0.8% versus 1.2%) rates., Conclusions: The use of a prognostic assessment and management pathway was effective in reducing the LOS for acute PE., Competing Interests: Conflict of interest: D. Jiménez has served as an advisor or consultant for Bayer HealthCare Pharmaceuticals, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Leo Pharma, Pfizer, ROVI and Sanofi; served as a speaker or a member of a speakers’ bureau for Bayer HealthCare Pharmaceuticals, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Leo Pharma, ROVI and Sanofi; and has received grants for clinical research from Daiichi Sankyo, Sanofi and ROVI. Conflict of interest: C. Rodríguez has nothing to disclose. Conflict of interest: F. León has nothing to disclose. Conflict of interest: L. Jara-Palomares has served as an advisor or consultant for Actelion Pharmaceuticals, Bayer HealthCare Pharmaceuticals, Leo Pharma, Menarini, Pfizer, GSK and ROVI. Conflict of interest: R. López-Reyes has nothing to disclose. Conflict of interest: P. Ruiz-Artacho has nothing to disclose. Conflict of interest: T. Elías has nothing to disclose. Conflict of interest: R. Otero has served as an advisor or consultant for Bayer HealthCare Pharmaceuticals, Leo Pharma, Janssen Pharmaceutical Companies, Merck Sharp & Dohme Corp, ROVI and Sanofi; and received grants for clinical research from Leo Pharma and Bayer Hispania SL. Conflict of interest: A. García-Ortega has nothing to disclose. Conflict of interest: A. Rivas-Guerrero has nothing to disclose. Conflict of interest: J. Abelaria has nothing to disclose. Conflict of interest: S. Jiménez has nothing to disclose. Conflict of interest: A. Muriel has nothing to disclose. Conflict of interest: R. Morillo has nothing to disclose. Conflict of interest: D. Barrios has nothing to disclose. Conflict of interest: R. Le Mao has nothing to disclose. Conflict of interest: R.D. Yusen has received research funding from Bayer HealthCare Pharmaceuticals, Bristol-Myers Squibb, Pfizer and Portola in the past 3 years; and has served as a consultant for Bayer HealthCare, Inc., Bristol-Myers Squibb, GlaxoSmithkline, Janssen, Johnson and Johnson, Ortho Pharmaceuticals, Organon, Pfizer, Portola, Sanofi and SCIOS in the past 3 years. Conflict of interest: B. Bikdeli reports that he is a consulting expert, on behalf of the plaintiff, for litigation related to two specific brand models of inferior vena cava filters. Conflict of interest: M. Monreal has served as an advisor or consultant for Bayer HealthCare Pharmaceuticals, Daiichi Sankyo, Leo Pharma and Sanofi; served as a speaker or a member of a speakers’ bureau for Bayer HealthCare Pharmaceuticals, Daiichi Sankyo, Leo Pharma and Sanofi; and received grants for clinical research from Sanofi and Bayer. Conflict of interest: J.L. Lobo has nothing to disclose., (Copyright ©The authors 2022. For reproduction rights and permissions contact permissions@ersnet.org.)

This position paper provides a comprehensive guide for optimal follow-up of patients with acute pulmonary embolism (PE), covering multiple relevant aspects of patient counselling. It serves as a practical guide to treating patients with acute PE complementary to the formal 2019 European Society of Cardiology guidelines developed with the European Respiratory Society. We propose a holistic approach considering the whole spectrum of serious adverse events that patients with acute PE may encounter on the short and long run. We underline the relevance of assessment of modifiable risk factors for bleeding, of acquired thrombophilia and limited cancer screening (unprovoked PE) as well as a dedicated surveillance for the potential development of chronic thromboembolic pulmonary hypertension as part of routine practice; routine testing for genetic thrombophilia should be avoided. We advocate the use of outcome measures for functional outcome and quality of life to quantify the impact of the PE diagnosis and identify patients with the post-PE syndrome early. Counselling patients on maintaining a healthy lifestyle mitigates the risk of the post-PE syndrome and improves cardiovascular prognosis. Therefore, we consider it important to discuss when and how to resume sporting activities soon after diagnosing PE. Additional patient-relevant topics that require Focused counselling are travel and birth control., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Importance: Active search for pulmonary embolism (PE) may improve outcomes in patients hospitalized for exacerbations of chronic obstructive pulmonary disease (COPD)., Objective: To compare usual care plus an active strategy for diagnosing PE with usual care alone in patients hospitalized for COPD exacerbation., Design, Setting, and Participants: Randomized clinical trial conducted across 18 hospitals in Spain. A total of 746 patients were randomized from September 2014 to July 2020 (final follow-up was November 2020)., Interventions: Usual care plus an active strategy for diagnosing PE (D-dimer testing and, if positive, computed tomography pulmonary angiogram) (n = 370) vs usual care (n = 367)., Main Outcomes and Measures: The primary outcome was a composite of nonfatal symptomatic venous thromboembolism (VTE), readmission for COPD, or death within 90 days after randomization. There were 4 secondary outcomes, including nonfatal new or recurrent VTE, readmission for COPD, and death from any cause within 90 days. Adverse events were also collected., Results: Among the 746 patients who were randomized, 737 (98.8%) completed the trial (mean age, 70 years; 195 [26%] women). The primary outcome occurred in 110 patients (29.7%) in the intervention group and 107 patients (29.2%) in the control group (absolute risk difference, 0.5% [95% CI, -6.2% to 7.3%]; relative risk, 1.02 [95% CI, 0.82-1.28]; P = .86). Nonfatal new or recurrent VTE was not significantly different in the 2 groups (0.5% vs 2.5%; risk difference, -2.0% [95% CI, -4.3% to 0.1%]). By day 90, a total of 94 patients (25.4%) in the intervention group and 84 (22.9%) in the control group had been readmitted for exacerbation of COPD (risk difference, 2.5% [95% CI, -3.9% to 8.9%]). Death from any cause occurred in 23 patients (6.2%) in the intervention group and 29 (7.9%) in the control group (risk difference, -1.7% [95% CI, -5.7% to 2.3%]). Major bleeding occurred in 3 patients (0.8%) in the intervention group and 3 patients (0.8%) in the control group (risk difference, 0% [95% CI, -1.9% to 1.8%]; P = .99)., Conclusions and Relevance: Among patients hospitalized for an exacerbation of COPD, the addition of an active strategy for the diagnosis of PE to usual care, compared with usual care alone, did not significantly improve a composite health outcome. The study may not have had adequate power to assess individual components of the composite outcome., Trial Registration: ClinicalTrials.gov Identifier: NCT02238639.

Background: The aim was to analyze the temporal relationship between short-term air pollution exposure and acute symptomatic unprovoked pulmonary embolism (PE)., Patients/methods: We performed a prospective, multicenter study in consecutive patients diagnosed with acute symptomatic unprovoked PE from February 2012 to January 2013. We analyzed demographic and clinical data, patients' addresses, meteorological and air pollutants data (PM 10 , SO 2 , CO, NO 2 , ozone emission data). We considered the number of days the patient had symptoms, and the study period constituted the previous 30 days. Likewise, the mean annual data of the reference season were calculated as well as the data of the 30-day study period corresponding to the same dates in the previous 3 years in order to obtain the monthly mean of the different pollutants for each period., Results: A total of 162 patients with acute symptomatic PE were recruited (43.2% unprovoked PE). The air pollutants could be determined in 50% of the patients with unprovoked PE, and a final analysis was performed in 35 patients. In the multiple comparison analysis to verify a possible correlation between the study period and the annual median, only NO 2 showed a statistically significant association (p = 0.009). When comparing the study period with the previous 3 years, only NO 2 maintained a statistically significant association for the 3 study periods., Conclusions: We found a relationship between short-term exposure to NO 2 and the presence of unprovoked PE., Competing Interests: Declaration of competing interest LJP reports personal fees from Bayer Hispania, Actelion, Rovi, PFIZER, Menarini, and Leo-Pharma, outside the submitted work. RO reports Grant support from Leo-Pharma and Bayer HealthCare-Fees for serving on advisory boards and giving lectures from Leo-Pharma, Rovi, Bayer HealthCare, MSD and Actelion. There is no other conflict of interest., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

In young patients with acute pulmonary embolism (PE), the predictive value of currently available prognostic tools has not been evaluated. Our objective was to compare prognostic value of 7 available tools (GPS, PESI, sPESI, Prognostic Algorithm, PREP, shock index and RIETE) in patients aged <50 years. We used the RIETE database, including PE patients from 2001 to 2017. The major outcome was 30-day all-cause mortality. Of 34,651 patients with acute PE, 5,822 (17%) were aged <50 years. Of these, 83 (1.4%) died during the first 30 days. Number of patients deemed low risk with tools was: PREP (95.9%), GPS (89.6%), PESI (87.2%), Shock index (70.9%), sPESI (59.4%), Prognostic algorithm (58%) and RIETE score (48.6%). The tools with a highest sensitivity were: Prognostic Algorithm (91.6%; 95% CI: 85.6-97.5), RIETE score (90.4%; 95%CI: 84.0-96.7) and sPESI (88%; 95% CI: 81-95). The RIETE, Prognostic Algorithm and sPESI scores obtained the highest overall sensitivity estimates for also predicting 7- and 90-day all-cause mortality, 30-day PE-related mortality, 30-day major bleeding and 30-day VTE recurrences. The proportion of low-risk patients who died within the first 30 days was lowest using the Prognostic Algorithm (0.2%), RIETE (0.3%) or sPESI (0.3%) scores. In PE patients less 50 years, 30-day mortality was low. Although sPESI, RIETE and Prognostic Algorithm scores were the most sensitive tools to identify patients at low risk to die, other tools should be evaluated in this population to obtain more efficient results.

Background: Unprovoked venous thromboembolism (VTE) may be the first manifestation of an underlying cancer. We aimed to assess the period prevalence of occult cancer detection stratified by VTE location (deep vein thrombosis [DVT], pulmonary embolism [PE] or both) and the anatomical relationship between occult cancer and VTE., Methods: Post-hoc analysis of a systematic review and individual patient data meta-analysis of adults with unprovoked VTE with at least 12 months of follow-up. Cancer types were grouped according to thoracic, abdomino-pelvic, or other locations., Results: A total of 2300 patients were eligible including 1218 with DVT only (53%), 719 with PE only (31%), and 363 with both PE and DVT (16%). The pooled 12-month period prevalence of cancer in DVT only, PE only, and DVT + PE was 5.6% (95% CI, 4.4 to 7.2), 4.3% (95% CI, 2.7 to 6.9), and 5.6% (95% CI, 1.7 to 15.5), respectively. Most occult cancers were located in the abdomen (68.4%). The proportion of patients with an abdomino-pelvic cancer was not different in patients with DVT + PE (81%; 95% CI, 54 to 96) than in those with DVT (68%; 95% CI, 57 to 78) or PE alone (65%; 95% CI, 48 to 79)., Conclusion: The 12-month prevalence of occult cancer was similar in patients with DVT only, PE only, or both. Most cancers were located in the abdomen, and there was no relationship between VTE type and cancer location., (Crown Copyright © 2019. Published by Elsevier Ltd. All rights reserved.)

Introduction: Some previous studies have suggested a high prevalence of pulmonary embolism (PE) during exacerbations of chronic obstructive pulmonary disease (ECOPD). The SLICE trial aims to assess the efficacy and safety of an active strategy for the diagnosis and treatment of PE (vs usual care) in patients hospitalized because of ECOPD., Methods: SLICE is a phase III, prospective, international, multicenter, randomized, open-label, and parallel-group trial. A total of 746 patients hospitalized because of ECOPD will be randomized in a 1:1 fashion to receive either an active strategy for the diagnosis and anticoagulant treatment of PE or usual care (ie, standard care without any diagnostic test for diagnosing PE). The primary outcome is a composite of all-cause death, non-fatal (recurrent) venous thromboembolism (VTE), or readmission for ECOPD within 90 days after enrollment. Secondary outcomes are (a) death from any cause within 90 days after enrollment, (b) non-fatal (recurrent) VTE within 90 days after enrollment, (c) readmission within 90 days after enrollment, and (d) length of hospital stay., Results: Enrollment started in September 2014 and is expected to proceed until 2020. Median age of the first 443 patients was 71 years (interquartile range, 64-78), and 26% were female., Conclusions: This multicenter trial will determine the value of detecting PEs in patients with ECOPD. This has implications for COPD patient morbidity and mortality., Trial Registration Number: NCT02238639., (© 2019 The Authors. Clinical Cardiology published by Wiley Periodicals, Inc.)

The impact of adherence to published guidelines on the outcomes of patients with acute pulmonary embolism (PE) has not been well defined by previous studies.In this prospective cohort study of patients admitted to a respiratory department (n=2096), we evaluated whether patients with PE had better outcomes if they were acutely managed according to international guidelines. Outcomes consisted of all-cause mortality, PE-related mortality, recurrent venous thromboembolism (VTE) and major bleeding events during the first month of follow-up after diagnosis.Overall, 408 patients (19% (95% CI 18-21%)) did not receive guideline-adherent PE management. Patients receiving non-adherent management were significantly more likely to experience all-cause mortality (adjusted odds ratio (OR) 2.39 (95% CI 1.57-3.61) or PE-related mortality (adjusted OR 5.02 (95% CI 2.42-10.42); p<0.001) during follow-up. Non-adherent management was also a significant independent predictor of recurrent VTE (OR 2.19 (95% CI 1.11-4.32); p=0.03) and major bleeding (OR 2.65 (95% CI 1.66-4.24); p<0.001). An external validation cohort of 34 380 patients with PE from the RIETE registry confirmed these findings.PE management that does not adhere to guidelines for indications related to anticoagulation, thrombolytics and inferior vena cava filters is associated with worse patient outcomes., Competing Interests: Conflict of interest: None declared., (Copyright ©ERS 2018.)

Objective: Clinical presentation and short-term prognosis of patients with travel-associated acute pulmonary embolism (PE) (i.e., economy class syndrome [ECS]) is not well understood., Methods: In this retrospective cohort study of patients with acute PE identified from a single center registry, we assessed the clinical presentation and the association between ECS and the outcomes of all-cause mortality, PE-related mortality, nonfatal venous thromboembolism and nonfatal major bleeding rates through 30days after initiation of PE treatment., Results: Of the 2,333 patients with acute symptomatic PE, 124 (5.3%; 95% confidence interval, 4.4-6.3%) had ECS. Patients with ECS were younger and had fewer comorbid diseases (recent bleeding, chronic obstructive pulmonary disease, congestive heart failure), but they presented with more signs of clinical severity (syncope [48% vs. 14%; P<.001], tachycardia [37% vs. 21%; P<.001], right ventricular dysfunction [31% vs. 19%; P<.01] and myocardial injury [57% vs. 28%; P<.001]) compared to those without ECS. Regression analyses showed a significantly lower risk of all-cause mortality for patients with ECS compared to patients without ECS (1.6% vs. 9.6%; P<.01). We did not detect a difference in PE-related mortality at 30days between those with and those without ECS (0.8% vs. 3.1%; P=.18)., Conclusions: PE patients with ECS are younger and have fewer comorbid diseases compared to those without ECS. Though they present with more signs of clinical severity, their short-term prognosis is excellent., (Copyright © 2017 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.)

Background: The benefits of a diagnostic workup for occult cancer in patients with VTE are controversial. Our aim was to provide and validate a risk score for occult cancer in patients with VTE., Methods: We designed a nested case-control study in a cohort of patients with VTE included in the RIETE (Registro Informatizado Enfermedad TromboEmbólica) registry from 2001 to 2014. Cases included cancer detected beyond the first 30 days and up to 24 months after VTE. Control subjects were defined as patients with VTE with no cancer in the same period., Results: Of 5,863 eligible patients, 444 (7.6%; 95% CI, 6.8%-8.2%) were diagnosed with occult cancer. On multivariable analysis, variables selected were male sex, age > 70 years, chronic lung disease, anemia, elevated platelet count, prior VTE, and recent surgery. We built a risk score assigning points to each variable. Internal validity was confirmed using bootstrap analysis. The proportion of patients with cancer who scored ≤ 2 points was 5.8% (241 of 4,150) and that proportion in those who scored ≥ 3 points was 12% (203 of 1,713). We also identified scores divided by sex and age subgroups., Conclusions: This is the first risk score that has identified patients with VTE who are at increased risk for occult cancer. Our score needs to be externally validated., (Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: The relationship between environmental factors and pulmonary embolism (PE) has received little attention. The aim of this study was to estimate the influence of climatological factors and air pollution levels on PE in Spain from 2001 to 2013., Methods: We carried out a retrospective study. Data were collected from the Minimum Basic Data Set (MBDS) and the State Meteorological Agency (AEMET) of Spain. A case-crossover analysis was applied to identify environmental risk factors related to hospitalizations and deaths. For each patient, climatic and pollutant factors were assigned using data from the meteorological station closest to his/her postal code., Results: A seasonal effect for PE hospital admission was observed, with more frequent admissions noted during Spain's colder seasons with peaks in autumn and winter. Lower temperatures as well as higher concentrations of NO2 and O3 at the time of admission (when 2weeks and 3weeks respectively were used as controls) were significant risk factors for hospital admissions with PE., Conclusions: Pulmonary embolism epidemiology was adversely influenced by colder climatological factors (absolute temperature, and seasonality) and higher concentrations of ambient air pollution (NO2, O3)., (Copyright © 2016 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Background: Strategies for identifying normotensive patients with acute symptomatic PE at high risk of PE-related complications remain to be defined., Methods: This prospective cohort study aimed to determine the role of plasma lactate levels in the risk assessment of normotensive patients with acute PE. Outcomes assessed over the 7 days after the diagnosis of PE included PE-related mortality and haemodynamic collapse, defined as need for cardiopulmonary resuscitation, systolic blood pressure <90 mm Hg for at least 15 min, need for catecholamine administration, or need for mechanical ventilation., Results: Between December 2012 and January 2014, the study enrolled 496 normotensive outpatients with acute symptomatic PE. PE-related complications occurred in 20 (4.0%; 95% CI 2.5% to 6.2%) of the 496 patients. These patients had higher baseline lactate levels (median 2.66 mmol/L; IQR 1.56-5.96 mmol/L) than patients without complications (1.20 mmol/L; IQR 1.20-2.00 mmol/L) (p<0.001). Overall, 135 patients (27.2%) had plasma lactate ≥2 mmol/L. Fourteen (10.4%) of them had PE-related complications versus 6 of 361 patients with low lactate (negative predictive value 98.3%; p<0.001). Patients with elevated plasma lactate had an increased rate of PE-related complications (adjusted OR 5.3; 95% CI 1.9 to 14.4; p=0.001) compared with those with low lactate. The combination of elevated plasma lactate with markers of right ventricular dysfunction (by echocardiogram) and myocardial injury (by cardiac troponin) was a particularly useful prognostic indicator (positive predictive value 17.9%; 95% CI 6.1% to 36.9%)., Conclusions: Plasma lactate represents a powerful predictor of short-term PE-related complications and may provide guidance for decision-making in PE care., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Introduction: Randomized clinical trials have demonstrated non-inferiority of rivaroxaban compared with vitamin K antagonists (VKAs) in the treatment of venous thromboembolism (VTE). Our objective was to analyze in real life, tolerance, recurrence, bleeding and adverse events of rivaroxaban in patients with acute symptomatic VTE., Material and Methods: Open follow-up study of a cohort of patients aged 18 and over diagnosed with deep vein thrombosis (DVT) and/or pulmonary embolism (PE) treated with rivaroxaban from December 2011 to January 2014., Results: The total number of patients treated with rivaroxaban was 103. The mean age was 58+/-17 years. The most frequent co-morbidities were: hypertension (30.0%), dyslipidemia (23.3%) and respiratory disease (25.2%). The type of thromboembolic event treated was: DVT (64.1%), PE (18.4%), DVT+PE (17.5%). Of the rivaroxaban-treated patients, 30% did so from the initial anticoagulant therapy and the other 70% in long-term or extended anticoagulant therapy. The median time of treatment with rivaroxaban was 6 months [corrected]. There was one recurrence and no deaths occurred. Six patients had bleeding, one of which was severe., Conclusions: Rivaroxaban provides a therapeutic alternative in a group of patients with VTE with advantages over VKAs, because of the convenience in dosing, lack of requirements for periodic monitoring and limited interaction with other drugs., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Although patent foramen ovale is a relatively common disease, the presence of paradoxical embolism is a rare clinical condition, representing less than 2% of arterial ischemias. We report the case of a 55-year-old male diagnosed with massive pulmonary embolism and paradoxical embolism in the right arm, secondary to patent foramen ovale. We also highlight some uncertainties in the diagnosis and treatment of patients with paradoxical embolism., (Copyright © 2013 SEPAR. Published by Elsevier Espana. All rights reserved.)

We report on a 20 year-old woman diagnosed with pulmonary embolism (PE) and right subclavian vein thrombosis attributable to stasis caused by right clavicular prominence. At the 10-months follow-up, the patient had developed chronic thromboembolic pulmonary hypertension (CTEPH), and treatment was begun with a dual endothelin receptor antagonist. Very few cases of deep venous thrombosis of upper limb have been reported in relation to anatomical abnormalities. This case is also exceptional because the patient developed a chronic thromboembolic pulmonary hypertension, whose incidence is estimated at 0.5% of all symptomatic PE., (Copyright © 2011 SEPAR. Published by Elsevier Espana. All rights reserved.)

Objectives: To analyse survival rate after 24 months in consecutive patients with a diagnosis of PE as well as associated factors., Methods: Prospective cohort study during a follow-up period of two years in a series of consecutive patients with PE., Results: During the follow-up period, 34 out of 148 patients died (23%). Factors independently associated with reduced survival rate were: creatinine levels > 2 (OR, 8.8; 95% CI, 1.1 - 70.87), previous neoplasm (OR, 8.8; 95% CI, 3.69 - 20.98), dementia (OR, 6.85; 95% CI, 2.1 - 22.33) and dyslipidemia (OR, 5.07; 95% CI, 1.92 - 13.44). Forty four percent of the patients with dyslipidemia died vs. 20.8% of patients without this condition., Conclusions: In our study dyslipidemia shows as a long-term negative prognostic marker for survival in patients with EP., (Copyright © 2011 Sociedade Portuguesa de Pneumologia. Published by Elsevier España. All rights reserved.)

We report the case of a 28-year-old woman taking contraceptives diagnosed with pulmonary embolism with a mass in the right atrium demonstrated by trans-thoracic echocardiogram that was not recognized on a previous angio-CT. Initially, it was thought to be a thrombus, but trans-oesophageal echocardiography and cardiac MRI showed data suggestive of cardiac neoplasm. Pericardial effusion and adjacent myocardial wall thickening noted on trans-oesophageal echocardiography were reported as signs that supported the possibility of malignancy, although cardiac MRI did not show wall infiltration signs. On the contrary, it demonstrated enhancement, which excludes the thrombotic nature of the mass and supports the diagnosis of neoplasm. The patient underwent surgery and biopsy proved that the mass was a myxoma. While myxomas are the most common among primary cardiac tumors, its attachment to the atrium free wall, far from the inter-atrium septum, the bi-lobed shape and accompanying pericardial effusion were atypical.

Introduction: An association between pulmonary embolism (PE) and a subsequent diagnosis of cancer has been repeatedly reported. Although screening and early detection might play a pivotal part in reducing mortality from cancer, there are currently no definite data to suggest that cancer screening may improve survival rates in patients with PE. We hereby present the results of a screening program and a two-year follow-up survey for detecting occult cancer in this patient population., Materials and Methods: A total of 107 patients with PE were consecutively enrolled. All subjects underwent an initial screening program followed by a two-year follow-up survey. We calculated the sensitivity of our screening program, and identified risk factors associated with occult cancer by means of logistic regression., Results: The initial screening program yielded positive results in five patients (4.7%), and four additional cases were identified during the 2-year follow-up. The overall sensitivity of our screening program in idiopathic PE was 55.5%. In the entire study cohort, the number necessary for screening was 12.1 (6.1 in idiopathic PE, and 58 in secondary PE). Logistic regression analysis revealed that a shock index >/=1 (odds ratio: 5.467; p=0.007) and idiopathic PE (odds ratio: 12.82; p=0.03) were independent risk factors for occult cancer in our PE patients., Conclusions: A simple and noninvasive screening program yields an acceptable sensitivity for detecting occult cancer in idiopathic PE patients. These results highlight the importance of screening for occult cancer in patients diagnosed with PE, especially in idiopathic forms., (Copyright 2009 Elsevier Ltd. All rights reserved.)

The relationship between cancer and venous thromboembolic disease (VTD) are complex because the activated coagulation factors are not only involved in thrombosis but also in malignant processes, such as angiogenesis and metastasis. To compare phenotypes of extracellular vesicles (EVs), and levels of D-dimer, soluble P-selectin (sP-selectin) and antigenic tissue factor (TF) between unprovoked VTD patients, who did not develop cancer during one-year follow-up, and those with advanced stage of cancer but not associated with VTD. A prospective study in which we included 138 unprovoked VTD patients and 67 advanced cancer patients, who did not develop thrombosis. Levels of EVs of different cellular origin (platelet, endothelium and leukocyte), EVs positive for tissue factor (TF) and P-selectin glycoprotein ligand 1 were quantified by flow cytometry. D-dimer, soluble P-selectin (sP-selectin) and antigenic TF were determined by ELISA. TF-positive EVs, D-dimer, and sP-selectin were markedly elevated in unprovoked VTD patients compared to cancer patients without association with thrombosis. Levels of TF-positive EVs, D-dimer and sP-selectin are able to discriminate between unprovoked VTD patients not related to cancer and cancer patients not associated with VTD. These results could lead to the application of EVs as biomarkers of both diseases. Key messages: Circulating EVs, specifically TF-positive EVs, in combination with plasmatic markers of hypercoagulable states, such as D-dimer, sP-selectin and antigen TF, are able to discriminate between cancer patients without thrombosis and patients with unprovoked VTD. Research fields could be opened. Future studies will assess if these biomarkers together serve as predicting thrombotic events in cancer populations [ABSTRACT FROM AUTHOR]