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Henrik Toft Sørensen,1 Nils Skajaa,1 Frederikus Albertus Klok,2 Kristina Laugesen,1 Dóra Körmendiné Farkas1 1Department of Clinical Epidemiology, Aarhus University Hospital and Aarhus University, Aarhus N, DK-8200, Denmark; 2Department of Medicine - Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, the NetherlandsCorrespondence: Henrik Toft Sørensen, Department of Clinical Epidemiology, Aarhus University, Olof Palmes Allé 43-45, Aarhus N, DK-8200, Denmark, Email hts@clin.au.dkBackground: Strong evidence indicates that venous thromboembolism is a presenting symptom of cancer. Cancer is a known cause of pulmonary hypertension; however, it remains unknown whether pulmonary hypertension is a marker of occult cancer. We examined the association between a pulmonary hypertension diagnosis and cancer risk in a cohort study using population-based data from the Danish health system.Patients and Methods: Using Danish nationwide registries, we identified 6335 patients with a pulmonary hypertension diagnosis and without a previous cancer diagnosis between 1995 and 2017. We computed the age-, sex-, and calendar year-standardized incidence ratio (SIR) as the ratio of observed to expected number of cancers using national incidence rates as the reference. We performed a subgroup analysis among patients with chronic thromboembolic pulmonary hypertension in the period in which a specific ICD-10 code was available (2006– 2017).Results: We identified 212 cancers within the first year of follow-up and 796 cancers thereafter. The one-year risk of cancer was 3.3% and the one-year SIR was 1.96 (95% confidence interval [CI]: 1.70– 2.23). In the second and subsequent years, the SIR remained elevated (SIR: 1.15 [95% CI: 1.08– 1.24]). In patients with chronic thromboembolic pulmonary hypertension, the one-year SIR was 1.41 (95% CI: 0.82– 2.25).Conclusion: Cancer risk was clearly higher in patients with pulmonary hypertension compared with the general population. The association was particularly strong in the first year of follow-up, but remained elevated thereafter. However, absolute risks were low, limiting the clinical relevance of pursuing early cancer detection in these patients.Keywords: pulmonary hypertension, chronic thromboembolic pulmonary hypertension, venous thrombosis, pulmonary embolism, cancer, cohort

AIM: To evaluate recovery of cardiac function after acute pulmonary embolism (PE). MATERIALS AND METHODS: Routine breath-held computed tomography (CT)-pulmonary angiography was performed in patients with suspected PE to confirm or exclude the diagnosis of PE at initial presentation. Electrocardiogram (ECG)-triggered cardiac CT was performed to assess biventricular function. After 6 months, cardiac magnetic resonance imaging (MRI) was performed. In total, 15 consecutive patients with PE and 10 without were studied. A significant change in ventricular volume was defined as a >15% change in end-diastolic or -systolic volumes (EDV, ESV), and significant ventricular function improvement as a >5% increase in ejection fraction (EF) as based on reported cut-off values. RESULTS: Right and left ventricular (RV and LV) EDV and ESV changed non-significantly (<1.3%) in the patients without PE, indicating good comparability of those values measured by CT and MRI. PE patients with baseline normal RV function (RVEF >=47%) revealed a >5% improvement in the RVEF (+5.4±3.1%) due to a decrease in the RVESV. Patients with baseline abnormal RV function showed a >5% improvement in the RVEF (+14±15%) due to decreases in both the RVESV and RVEDV. Furthermore, the LVEDV increased in this latter patient group. CONCLUSIONS: The present study demonstrated an improvement in RV function in the majority of patients with PE, independent of baseline RV function. The degree of RV and LV recovery was dependent on the severity of baseline RV dysfunction. [ABSTRACT FROM AUTHOR]

Background: Right ventricular (RV) function is predictive of outcome in patients with acute pulmonary embolism (PE). We assessed the possible incremental value of ventricular function with ECG-synchronized cardiac CT scanning over pulmonary CT scan angiography (CTA) for predicting short-term outcome in patients with suspected acute PE.Methods: The local ethics committee approved the study, and informed consent was obtained. In addition to standard CTA, 430 consecutive patients (193 men, 237 women; age, 55 ± 17 years) with suspected acute PE underwent ECG-synchronized CT scanning to assess ventricular function. RV/left ventricular (LV) function ratio and pulmonary obstruction index were obtained from non-ECG-synchronized CTA. Ventricular function was used to predict adverse events (< 6 weeks). Receiver operating characteristic analysis was performed to determine differences between ECG-synchronized CT scan and CTA in predicting outcome.Results: In 113 patients with PE, RV and LV ejection fraction (EF) and RV/LV diameter and volume ratios were associated with adverse outcome (P < .05), whereas vascular obstruction index was not. RVEF had the largest area under the receiver operating characteristic curve (0.75; 95% CI, 0.62-0.88) for predicting adverse outcome but had no significant incremental value over the RV/LV function ratio (0.72; 95% CI, 0.57-0.86; P = .25). All parameters revealed high negative predictive values (94%-98%) but low positive predictive values (13%-18%). For disease-specific outcome, areas under the curve were 0.80 (95% CI, 0.69-0.91) for RVEF vs 0.68 (95% CI, 0.48-0.88) for axial RV/LV ratio; the difference was not significant (P = .07). RVEF and RV/LV ratio proved better predictors for outcome than pulmonary obstruction index (both P < .001).Conclusions: RVEF was the best predictor for clinical outcome in patients with acute PE. However, incremental value of RVEF over axial RV/LV ratio was not found. [ABSTRACT FROM AUTHOR]

Background: Several clinical decision rules (CDRs) are available to exclude acute pulmonary embolism (PE), but they have not been directly compared. Objective: To directly compare the performance of 4 CDRs (Wells rule, revised Geneva score, simplified Wells rule, and simplified revised Geneva score) in combination with d-dimer testing to exclude PE. Design: Prospective cohort study. Setting: 7 hospitals in the Netherlands. Patients: 807 consecutive patients with suspected acute PE. Intervention: The clinical probability of PE was assessed by using a computer program that calculated all CDRs and indicated the next diagnostic step. Results of the CDRs and d-dimer tests guided clinical care. Measurements: Results of the CDRs were compared with the prevalence of PE identified by computed tomography or venous thromboembolism at 3-month follow-up. Results: Prevalence of PE was 23%. The proportion of patients categorized as PE-unlikely ranged from 62% (simplified Wells rule) to 72% (Wells rule). Combined with a normal d-dimer result, the CDRs excluded PE in 22% to 24% of patients. The total failure rates of the CDR and d-dimer combinations were similar (1 failure, 0.5% to 0.6% [upper-limit 95% CI, 2.9% to 3.1%]). Even though 30% of patients had discordant CDR outcomes, PE was not detected in any patient with discordant CDRs and a normal d-dimer result. Limitation: Management was based on a combination of decision rules and d-dimer testing rather than only 1 CDR combined with d-dimer testing. Conclusion: All 4 CDRs show similar performance for exclusion of acute PE in combination with a normal d-dimer result. This prospective validation indicates that the simplified scores may be used in clinical practice. Primary Funding Source: Academic Medical Center, VU University Medical Center, Rijnstate Hospital, Leiden University Medical Center, Maastricht University Medical Center, Erasmus Medical Center, and Maasstad Hospital. [ABSTRACT FROM AUTHOR]

Rationale: There is a lack of information on the long-term prognosis of patients with acute pulmonary embolism (PE). Objectives: To assess the long-term risk for adverse events after PE. Methods: Consecutive patients diagnosed with PE between January 2001 and July 2007, and patients in whom PE was ruled out from a previous study were followed until July 2008 for the occurrence of adverse clinical events: mortality, symptomatic recurrent venous thromboembolism, cancer, arterial cardiovascular events and chronic thromboembolic pulmonary hypertension. Hazard ratios (HR) for all endpoints and a combined endpoint were calculated and adjusted for potential confounders. Measurements and Main Results: Three hundred eight patients with unprovoked, 558 with provoked, and 334 without PE were studied with a median follow-up period of 3.3 years. Patients with unprovoked PE had a lower overall risk for mortality than patients with provoked PE (HR, 0.59; 95% confidence interval [CI], 0.43-0.82), but a higher risk for nonmalignancy-related mortality (HR, 1.8; 95% CI, 1.3-2.5), recurrent venous thromboembolism (HR, 2.1; 95% CI, 1.3-3.1), cancer (HR, 4.4; 95% CI, 2.0-10), cardiovascular events (HR, 2.6; 95% CI, 1.5-3.8) and chronic thromboembolic pulmonary hypertension (1.5 vs. 0%). The risk for the combined endpoint did not differ between both groups (HR, 0.98; 95% CI, 0.82-1.1). Patients without PE had similar risks for malignancy and cardiovascular events than patients with provoked PE, but lower risks for the remaining outcomes. The fraction of both patients with provoked and unprovoked PE without events after 1 year was only 70% and decreased to fewer than 60% after 2 years and fewer than 50% after 4 years, whereas this latter was 84% for the control patients. Conclusions: The clinical course of acute PE is complicated by high rates of serious adverse events, which occur in half of the patients within 4 years. [ABSTRACT FROM AUTHOR]

RATIONALE: The potential role of elevated brain-type natriuretic peptides (BNP) in the differentiation of patients suffering from acute pulmonary embolism at risk for adverse clinical outcome has not been fully established. OBJECTIVES: We evaluated the relation between elevated BNP or N-terminal-pro-BNP (NT-pro-BNP) levels and clinical outcome in patients with pulmonary embolism. METHODS: Articles reporting on studies that evaluated the risk of adverse outcome in patients with pulmonary embolism and elevated BNP or NT-pro-BNP levels were abstracted from Medline and EMBASE. Information on study design, patient and assay characteristics, and clinical outcome was extracted. Primary endpoints were overall mortality and predefined composite outcome of adverse clinical events. MEASUREMENTS AND MAIN RESULTS: Data from 13 studies were included. In 51% (576/1,132) of the patients, BNP or NT-pro-BNP levels were increased. The different analyses were performed in subpopulations. Elevated levels of BNP or NT-pro-BNP were significantly associated with right ventricular dysfunction (P < 0.001). Patients with high BNP or NT-pro-BNP concentration were at higher risk of complicated in-hospital course (odds ratio [OR], 6.8; 95% confidence interval [CI], 4.4-10) and 30-day mortality (OR, 7.6; 95% CI, 3.4-17). Patients with a high NT-pro-BNP had a 10% risk of dying (68/671; 95% CI, 8.0-13%), whereas 23% (209/909; 95% CI, 20-26%) had an adverse clinical outcome. CONCLUSIONS: High concentrations of BNP distinguish patients with pulmonary embolism at higher risk of complicated in-hospital course and death from those with low BNP levels. Increased BNP or NT-pro-BNP concentrations alone, however, do not justify more invasive treatment regimens. [ABSTRACT FROM AUTHOR]

Introduction: Managing older patients with acute pulmonary embolism (PE) is challenging due to their underrepresentation in clinical trials, comorbidities and increased complication risk. This study evaluates risk assessment and management outcomes in older PE patients focussing on home and reperfusion treatment., Methods: A retrospective analysis was conducted on patients aged ≥70 years diagnosed with acute PE at an academic medical centre (2015-2022)., Results: 242 patients with a mean age of 77 years were included. All 59 patients with negative Hestia criteria were discharged ≤24h, and in total 81 patients (35%) received home treatment. Among these 14-day mortality and recurrent venous-thromboembolism were 0% and major bleeding occurred in 1.3% (one patient, 95%CI 0.11-6.1). European Society of Cardiology (ESC) risk-classification showed 9 low-risk PE (3.9%), 199 intermediate-risk (87%), and 20 high-risk PE patients (8.8). In 5 of the 20 high-risk patients, hypotension was mainly caused by another condition, i.e. sepsis. Eight high-risk patients received reperfusion therapy. Fourteen-day mortality was 51% in high-risk patients (95%CI 27-71); 5 out of 8 patients receiving reperfusion treatment died within 5 days. Patients with an Acute Presenting Older Patient (APOP) score of ≥45% had higher 14-day mortality (28%; 95%CI 12-46) compared to <45% (3.2%; 95%CI 0.85-8.3; HR 10.2; 95%CI 2.6-39)., Conclusion: Selecting for home treatment using Hestia was safe for older PE patients in our cohort. Mortality in the high-risk group was high also when receiving reperfusion treatment. The ESC risk-classification and APOP score identified patients at higher mortality risk, suggesting their potential utility in clinical decision-making., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

COVID-19-related critical and acute illness are associated with an increased risk of venous thromboembolism (VTE). These evidence-based recommendations of the American Society of Hematology (ASH) are intended to support patients, clinicians, and other healthcare professionals in decisions about the use of anticoagulation for thromboprophylaxis in patients with COVID-19-related critical illness, acute illness, and those being discharged from the hospital, who do not have suspected or confirmed VTE. ASH formed a multidisciplinary panel, including three patient representatives, and applied a conflicts of interest management policy to minimize potential bias. The Michael G. DeGroote Cochrane Canada and MacGRADE Centres at McMaster University supported the guideline development process, including performing systematic evidence reviews (up to June 2023). The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients. The panel used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to assess certainty of the evidence and make recommendations, which were subject to public comment. This is an executive summary of three updated recommendations that have been published which concludes the living phase of the guidelines. For critically ill patients with COVID-19, the panel issued conditional recommendations in favor of (a) prophylactic-intensity over therapeutic-intensity anticoagulation and (b) prophylactic-intensity over intermediate-intensity anticoagulation. For acutely ill patients with COVID-19, conditional recommendations were made in favor of (a) prophylactic-intensity over intermediate-intensity anticoagulation and (b) therapeutic-intensity over prophylactic-intensity anticoagulation. The panel also issued a conditional recommendation against the use of post-discharge extended pharmacologic thromboprophylaxis. These three conditional recommendations were made based on low or very low certainty in the evidence, underscoring the need for additional, high-quality randomized controlled trials in patients with COVID-19-related illness., (Copyright © 2024 American Society of Hematology.)

Despite abundant clinical innovation and burgeoning scientific investigation, pulmonary embolism (PE) has continued to pose a diagnostic and management challenge worldwide. Aging populations, patients living with a mounting number of chronic medical conditions, particularly cancer, and increasingly prevalent health care disparities herald a growing burden of PE. In the meantime, navigating expanding strategies for immediate and long-term anticoagulation, as well as advanced therapies, including catheter-based interventions for patients with more severe PE, has become progressively daunting. Accordingly, clinicians frequently turn to evidence-based clinical practice guidelines for diagnostic and management recommendations. However, numerous international guidelines, heterogeneity in recommendations, as well as areas of uncertainty or omission may leave the readers and clinicians without a clear management pathway. In this review of international PE guidelines, we highlight key areas of consistency, difference, and lack of recommendations (silence) with an emphasis on critical clinical and research needs., Competing Interests: Funding Support and Author Disclosures Outside of the submitted work, Dr Bikdeli is supported by a Career Development Award from the American Heart Association and VIVA Physicians (#938814); was supported by the Scott Schoen and Nancy Adams IGNITE Award; is supported by the Mary Ann Tynan Research Scientist award from the Mary Horrigan Connors Center for Women’s Health and Gender Biology at Brigham and Women’s Hospital, and the Heart and Vascular Center Junior Faculty Award from Brigham and Women’s Hospital; was a consulting expert, on behalf of the plaintiff, for litigation related to 2 specific brand models of IVC filters (he has not been involved in the litigation in 2022-2024 nor has he received any compensation in 2022-2024); is a member of the Medical Advisory Board for the North American Thrombosis Forum; serves in the Data Safety and Monitory Board of the NAIL-IT trial funded by the National Heart, Lung, and Blood Institute, and Translational Sciences; and is a collaborating consultant with the International Consulting Associates and the U.S. Food and Drug Administration in study to generate knowledge about utilization, predictors, retrieval, and safety of IVC filters. Dr Barco has received institutional research support from Boston Scientific, Medtronic, Bayer, and Sanofi; and has received personal fees/honoraria from Boston Scientific, Penumbra, and Viatris. Dr Giannakoulas has received fees for lectures and/or consultations from Actelion/Janssen, Bayer, Boehringer Ingelheim, ELPEN Pharmaceuticals, Ferrer-Galenica, GlaxoSmithKline, Gossamer-Bio, Merck Sharp and Dohme, Pfizer, Lilly, and United Therapeutics. Dr Jimenez has served as a speaker for Bristol Myers Squibb, ROVI, and Sanofi. Dr Lang, in addition to being an investigator in trials involving these companies, has relationships including consultancy service, research grants, and membership of scientific advisory boards for drug companies including AOP-Health, Actelion-Janssen, Merck Sharp and Dohme, United Therapeutics, Medtronic, Neutrolis, and Novo Nordisk; has served as a consultant for AOP Health, Merck Sharp and Dohme, PULNOVO, United Therapeutics, and Janssen; has received grants from AOP Health; and has served on the Speakers Bureau for Merck Sharp and Dohme and Janssen. Dr Klok has received research funding from Bayer, Bristol Myers Squibb, BSCI, AstraZeneca, Merck Sharp and Dohme, 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 of this work and paid to his institution. Dr Weitz holds the Canada Research Chair (Tier 1) in Thrombosis and the Heart and Stroke Foundation J.F. Mustard Chair in Cardiovascular Research. Dr Piazza has received research grants (paid to his institution) from Bristol Myers Squibb/Pfizer, Janssen, Alexion, Bayer, Amgen, BSC, Esperion, and the National Institutes of Health (1R01HL164717-01); and has received consulting fees for advisory roles from BSC, Amgen, PERC, NAMSA, Bristol Myers Squibb, Janssen, Penumbra, and Thrombolex. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Despite uncertain benefit-risk profile near the end of life, antithrombotic therapy (ATT) is prevalent in patients with terminal cancer., Objectives: To examine adherence and persistence with ATT in terminally ill cancer patients and investigate risks of major and clinically relevant bleeding, venous thromboembolism (VTE), and arterial thromboembolism (ATE) by ATT exposure., Methods: Using a Danish nationwide cohort of terminal cancer patients, ATT adherence in the year following terminal illness declaration was measured by the proportion of days covered (PDC) by prescription. Discontinuation was defined as a treatment gap of ≥30 days between prescription renewals. One-year cumulative incidences of bleeding complications, VTE, and ATE were calculated, considering the competing risk of death., Results: During 2013-2022, 86,732 terminally ill cancer patients were identified (median age 75 years, 47% female, median survival 57 days). At terminal illness declaration, 37.5% were receiving ATT (66.6% platelet inhibitors, 23.0% direct oral anticoagulants (DOAC), and 10.4% vitamin K antagonists (VKA)). The mean PDC was 88% (SD 30%), highest among platelet inhibitor users (mean PDC 89%) and lowest among VKA users (73%). One-year ATT discontinuation incidence was 7.9% (95% CI 7.7%-8.1%). Most patients continued ATT until death (74.8% platelet inhibitors, 58.8% DOACs, 61.6% VKAs). Patients receiving ATT had a lower one-year VTE risk but higher risks of ATE and major bleeding., Conclusion: Despite uncertain benefit-risk profile, most terminally ill cancer patients continue ATT until the end of life. These findings provide insights into current ATT utilisation and discontinuation dynamics in the challenging context of terminal illness., (Copyright © 2024. Published by Elsevier Inc.)

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.)

Recent advances in therapy and the promulgation of multidisciplinary pulmonary embolism teams show great promise to improve management and outcomes of acute pulmonary embolism (PE). However, the absence of randomized evidence and lack of consensus leads to tremendous variations in treatment and compromises the wide implementation of new innovations. Moreover, the changing landscape of health care, where quality, cost, and accountability are increasingly relevant, dictates that a broad spectrum of outcomes of care must be routinely monitored to fully capture the impact of modern PE treatment. We set out to standardize data collection in patients with PE undergoing evaluation and treatment, and thus establish the foundation for an expanding evidence base that will address gaps in evidence and inform future care for acute PE. To do so, >100 international PE thought leaders convened in Washington, DC, in April 2022 to form the Pulmonary Embolism Research Collaborative. Participants included physician experts, key members of the US Food and Drug Administration, patient representatives, and industry leaders. Recognizing the multidisciplinary nature of PE care, the Pulmonary Embolism Research Collaborative was created with representative experts from stakeholder medical subspecialties, including cardiology, pulmonology, vascular medicine, critical care, hematology, cardiac surgery, emergency medicine, hospital medicine, and pharmacology. A list of critical evidence gaps was composed with a matching comprehensive set of standardized data elements; these data points will provide a foundation for productive research, knowledge enhancement, and advancement of clinical care within the field of acute PE, and contribute to answering urgent unmet needs in PE management. Evidence produced through the Pulmonary Embolism Research Collaborative, as it is applied to data collection, promises to provide crucial knowledge that will ultimately produce a robust evidence base that will lead to standardization and harmonization of PE management and improved outcomes., Competing Interests: Dr Rosenfield reports consulting fees from Abbott Vascular, Boston Scientific, Contego, Imperative Care, Johnson & Johnson, Biosense Webster, Medtronic, Neptune Medical, and Philips; board membership for the PERT (Pulmonary Embolism Response Team) Consortium; and stock or stock options in Access Vascular, Althea Medical, Auxetics, Contego, Endospan, Imperative Care, Innova Vascular, InspireMD, JanaCare, Magneto, MedAlliance, Neptune Medical, Orchestra, Sealonix, Shockwave, Skydance, Summa Therapeutics, Thrombolex, Vantis Vascular, Vasorum, Viz.ai, and Vumedi. Dr Bowers reports consulting fees from Truvic, Inc, lecture fees from Janssen and Bristol Myers Squibb (BMS)-Pfizer, payment for expert testimony, and participation on Advisory Board of Truvic, Inc. Dr Barnett reports payment for expert testimony. Dr Davis reports travel support for attending the Pulmonary Embolism Research Collaborative meeting. Dr Giri reports research support from Boston Scientific, Inc, and Inari Medical; consulting fees from Boston Scientific, Inc, Cordis, and Abbott Vascular; support for attending meetings from Inari Medical; participation on an advisory board for Angiodynamics, Inc, and Boston Scientific, Inc; participation in leadership at Society for Cardiac Angiography and Intervention and the PERT Consortium; and stock or stock options in Endovascular Engineering. Dr Horowitz reports research support from Inari Medical; consultation and personal lecture fees from Inari Medical and Penumbra, Inc; and support for attending meetings from Inari Medical. Dr Keeling reports consulting fees from Angiodynamics, Inc, Penumbra, Inc, Viz.ai, and Dexcom. Dr Klok reports institutional research support from Bayer, Bristol Myers Squibb, Actelion, Boston Scientific, Inc, Leo Pharma, the Netherlands Organisation for Health Research and Development, the Dutch Thrombosis Association, the Dutch Heart Foundation, and the Horizon Europe program; service on the Board of the Rembrandt Institute of Cardiovascular Science; Chair of the Board of the Dutch Society of Vascular Medicine; nucleus member of the European Society of Cardiology work group on pulmonary circulation and RV function; nucleus member of ISTH SSC diagnostic and predictive variables; Chair of the Board of the Dutch Thrombosis Network; and medical lead, Anticoagulation Clinic Leiden. Dr Konstantinides reports personal and institutional consulting fees from Bayer AG, Daiichi-Sankyo, and Boston Scientific, Inc, and personal lecture fees from Bayer AG, Daiichi-Sankyo, Pfizer–Bristol Myers Squibb, and Boston Scientific, Inc. Dr Lookstein reports consulting fees from Penumbra, Inc, Boston Scientific, Inc, Medtronic, Cordis, Becton Dickinson, Abbott Vascular, Neptune Medical, Imperative Care, and Aidoc; payment for expert testimony; participation on advisory boards for Magneto, Boston Scientific, Inc, Medtronic, and Trireme; leadership roles at the PERT Consortium, Critical Limb Ischemia Global Society, and Society of Interventional Radiology; and stock or stock options in Imperative Vascular, Thrombolex, Innova Vascular, and Summa Vascular. Dr Moriarty reports research support from Angiodynamics, Inc, and Penumbra, Inc; consulting fees from Angiodynamics, Inc, Penumbra Inc, Inquis Medical, Innova Vascular, Boston Scientific Inc, Auxetics, and Retriever Medical; and participation on the data safety monitoring board for Penumbra, Inc. Dr Ní Áinle reports institutional research support from Sanofi, Daiichi-Sankyo, the Irish Health Research Board, Bayer, and Boston Scientific, Inc; patents pending for European Application No. 20166826.6; past member of World Thrombosis Day International Steering Committee; Director at Large and Member, International Network of Venous ThromboEmbolism Research Networks Council; Co-Director, InVite; Co-Founder and member of Executive Committee of Venous Thromboembolism Ireland; Advisory Committee for Human Medicines; member of “Preventing Venous Thromboembolism in Hospitals” Collaborative Advisory Group; Board Member, Thrombosis Ireland Patient Organization and Charity; and National Lead, Irish Venous Thromboembolism Patient Safety Programme. Dr Rosovsky reports research support from BMS and Janssen; consulting fees from Abbott, BMS, Dova, Inari Medical, Janssen, and Penumbra, Inc; participation on the data safety monitoring board for the Pepper Trial and Harvard Cancer Center; unpaid President-Elect of the PERT Consortium; and unpaid member of ASH Committee on Quality. Dr Secemsky reports research support from NIH/NHLBINIH/NHBLI K23HL150290, Food and Drug Administration, Becton-Dickinson, Boston Scientific, Inc, Cook Medical, Cardiovascular Systems Inc., Laminate Medical, Medtronic, and Philip; consulting fees and personal lecture fees from Abbott, Bayer, Becton-Dickinson, Boston Scientific, Inc, Cook, Cardiovascular Systems Inc., Inari Medical, Medtronic, Philips, Shockwave, and VentureMed; and participation on data safety monitoring boards for LIFE BTK, BIOMIMCS3D, HI-PEITHO, and Transcend. Dr Sharp reports consulting and lecture fees from Medtronic, Boston Scientific, Inc, Philips, Recor Medical, and Penumbra, Inc. Dr Sista reports research support from NIH/NHLBI as principal investigator of U34 and UG3 awards, unpaid participation on data safety monitoring boards for Angiodynamics, Inc, and Thrombolex, Inc; and participation on the Board of Directors for the Society of Interventional Radiology. Dr Wells reports participation on the data safety monitoring board for Anthos. The other authors report no conflicts.

Background: A considerable number of patients with chronic thromboembolic pulmonary hypertension (CTEPH) lack a history of venous thromboembolism (VTE)., Objectives: We aimed to examine the annual incidence and prevalence of CTEPH in Denmark and to compare the rates of VTE, bleeding, and mortality between CTEPH patients with and without a history of VTE., Methods: The Danish National Patient Registry covering all Danish hospitals was used to identify all CTEPH cases between 2009 and 2018, based on combinations of discharge diagnoses using International Classification of Diseases, 10th Revision codes for CTEPH and relevant diagnostic and/or therapeutic interventions. Incidence rates of CTEPH per 100 000 person-years, rates of VTE and bleeding, and 5-year survival estimates were calculated., Results: In total, 509 CTEPH patients were identified, of whom 82% had a history of VTE. The yearly incidence rate of CTEPH was 0.5 to 0.8 per 100 000 person-years during the study period. Patients with a history of VTE experienced a 2.5-fold rate of VTE compared with those without prior VTE (2571 vs 980 per 100 000 person-years), while the rate of bleeding events was lower (5008 vs 7139 per 100 000 person-years). The 5-year survival of CTEPH patients with a VTE history was 65% (95% CI, 58%-71%) compared with 45% (95% CI, 31%-58%) in patients without a history of VTE., Conclusion: The Danish incidence rate of CTEPH was comparable with that of other European countries. We identified notable differences in the prognosis of patients with CTEPH with or without a history of VTE. These findings may support generation of hypotheses regarding the pathophysiology of CTEPH and inform current patient care., Competing Interests: Declaration of competing interests F.A.K. received research funding 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 work and paid to his institution. S.B. received institutional funding from Concept Medical, Boston Scientific, Medtronic, Bard, Bayer, Sanofi, Novartis, and Daiichi Sankyo. The Department of Clinical Epidemiology, Aarhus University and Aarhus University Hospital receive funding from private and public institutions in the form of research grants to (and administered by) Aarhus University. None of these grants has any relation to the present study. K.B. was supported by a research grant from the Danish Diabetes and Endocrine Academy, which is funded by the Novo Nordisk Foundation, grant number NNF22SA0079901. All other authors report no conflict of interest., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Deep vein thrombosis (DVT) is a cause of considerable morbidity worldwide. It is a common clinical disease in the daily practice of several medical disciplines including general medicine, angiology, and internal medicine, as well as of interest to public health because of its preventability and its sensitivity to secular changes in the distribution of population risk factors. In this review we present a comprehensive overview of the epidemiological features of DVT, including incidence and risk factors. Additionally, we give an overview of the burden that DVT poses on modern health care systems.

Introduction: Pulmonary infarction is a common sequela of pulmonary embolism (PE) but lacks a diagnostic reference standard. CTPA in the setting of acute PE does not reliably differentiate infarction from other consolidations, such as reversible alveolar hemorrhage or atelectasis. We aimed to assess the diagnostic accuracy for recognizing pulmonary infarction on CT in the acute phase of PE, with follow-up CT as reference., Materials and Methods: Initial and follow-up CT scans of 33 patients with acute PE were retrospectively assessed. Two radiologists independently evaluated the presence and size of suspected pulmonary infarction on the initial CT. Confirmation of infarction was established by detection of residual densities on follow-up CT. Sensitivity, specificity and interobserver variability were calculated., Results: In total, 60 presumed infarctions were found in 32 patients, of which 34 infarctions in 21 patients could be confirmed at follow-up. On patient-level, observers' sensitivity/specificity were 91 %/9 %, and 73 %/46 %, respectively, with interobserver agreement by Kappa's coefficient of 0.17. Confirmed infarctions were usually larger than false positive lesions (median approximate volume of 6.6 mL [IQR 0.84-21.3] vs. 1.3 mL [IQR 0.57-6.5], p = 0.040), but still small. An occluding thrombus in a supplying vessel was predictive for confirmed infarction (OR 11, 95%CI 2.1-55), but was not discriminative., Conclusions: Pulmonary infarction is a common finding in acute PE, and generally small. Radiological identification of infarction was challenging, with considerable interobserver variability. Complete obstruction of the supplying (sub)segmental pulmonary artery was found as the strongest predictor for pulmonary infarction but was not demonstrated to be discriminative., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: F.A.K. has received research support from Bayer, BMS, BSCI, MSD, Leo Pharma, Actelion, The Netherlands Organisation for Health Research and Development, The Dutch Thrombosis Association, The Dutch Heart Foundation and the Horizon Europe Program, all paid to his institution and independent of the current work. M.V.H. reports unrestricted grant support from The Netherlands Organisation for Health Research and Development (ZonMW), and unrestricted grant support and fees for presentations from Boehringer-Ingelheim, Pfizer-BMS, Bayer Health Care, Aspen, Daiichi-Sankyo, all outside the submitted work. The other authors have no conflicts of interest to declare., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Regarding adjustments to warfarin dosage, numerous studies have shown that computerized methods are superior to those based on personal experience., Objectives: To report the efficacy of a computer-based warfarin management system (WMS) in the Iranian population., Methods: By utilizing the existing dosing algorithms and obtaining expert opinions, we developed a computer-based WMS at a large tertiary cardiovascular center. The time in therapeutic range and the number of international normalized ratio (INR) tests of clinic patients were compared before and after the implementation of WMS., Results: Overall, 803 patients with 5407 INR tests were included in the before phase and 679 patients with 4189 INR tests in the after phase. The mean time in therapeutic range was 57.3% before and 59% after WMS implementation [mean difference, 1.64; 95% confidence interval (CI), -1.12-4.40]. In the before phase, the mean number of INR tests was 6.7, which dropped to 6.1 tests in the after phase (mean difference, -0.61; 95% CI, -0.97 to -0.24). Only 54.5% of the warfarin dosing prescriptions were consistent with the dosing recommendations of the WMS, and adherence to the WMS was poorest in the highest INR target range., Conclusions: For the first time in Iran, we demonstrated that a computerized system was as effective as a traditional experience-based method to monitor INR in VKA-anticoagulated patients. Furthermore, it could reduce both the number of INR tests and that of visits., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: To investigate the prevalence of cerebrovascular MRI markers in unselected patients hospitalized for COVID-19 (Coronavirus disease 2019), we compared these with healthy controls without previous SARS-CoV-2 infection or hospitalization and subsequently, investigated longitudinal (incidental) lesions in patients after three months., Methods: CORONIS (CORONavirus and Ischemic Stroke) was an observational cohort study in adult hospitalized patients for COVID-19 and controls without COVID-19, conducted between April 2021 and September 2022. Brain MRI was performed shortly after discharge and after 3 months. Outcomes included recent ischemic (DWI-positive) lesions, previous infarction, microbleeds, white matter hyperintensities (WMH) and intracerebral hemorrhage and were analysed with logistic regression to adjust for confounders., Results: 125 patients with COVID-19 and 47 controls underwent brain MRI a median of 41.5 days after symptom onset. DWI-positive lesions were found in one patient (1%) and in one (2%) control, both clinically silent. WMH were more prevalent in patients (78%) than in controls (62%) (adjusted OR: 2.95 [95% CI: 1.07-8.57]), other cerebrovascular MRI markers did not differ. Prevalence of markers in ICU vs. non-ICU patients was similar. After three months, five patients (5%) had new cerebrovascular lesions, including DWI-positive lesions (1 patient, 1.0%), cerebral infarction (2 patients, 2.0%) and microbleeds (3 patients, 3.1%)., Conclusion: Overall, we found no higher prevalence of cerebrovascular markers in unselected hospitalized COVID-19 patients compared to controls. The few incident DWI-lesions were most likely to be explained by risk-factors of small vessel disease. In the general hospitalized COVID-19 population, COVID-19 shows limited impact on cerebrovascular MRI markers shortly after hospitalization., (© 2024. The Author(s).)

Background: Guidelines suggest indefinite anticoagulation after unprovoked venous thromboembolism (VTE) unless the bleeding risk is high, yet there is no consistent guidance on assessing bleeding risk., Objectives: This study aimed to evaluate the performance of 5 bleeding risk tools (RIETE, VTE-BLEED, CHAP, VTE-PREDICT, and ABC-Bleeding)., Methods: PLATO-VTE, a prospective cohort study, included patients aged ≥40 years with a first unprovoked VTE. Risk estimates were calculated at VTE diagnosis and after 3 months of treatment. Primary outcome was clinically relevant bleeding, as per International Society on Thrombosis and Haemostasis criteria, during 24-month follow-up. Discrimination was assessed by the area under the receiver operating characteristic curve (AUROC). Patients were classified as having a "high risk" and "non-high risk" of bleeding according to predefined thresholds; bleeding risk in both groups was compared by hazard ratios (HRs)., Results: Of 514 patients, 38 (7.4%) had an on-treatment bleeding. AUROCs were 0.58 (95% CI, 0.48-0.68) for ABC-Bleeding, 0.56 (95% CI, 0.46-0.66) for RIETE, 0.53 (95% CI, 0.43-0.64) for CHAP, 0.50 (95% CI, 0.41-0.59) for VTE-BLEED, and 0.50 (95% CI, 0.40-0.60) for VTE-PREDICT. The proportion of high-risk patients ranged from 1.4% with RIETE to 36.9% with VTE-BLEED. The bleeding incidence in the high-risk groups ranged from 0% with RIETE to 13.0% with ABC-Bleeding, and in the non-high-risk groups, it varied from 7.7% with ABC-Bleeding to 9.6% with RIETE. HRs ranged from 0.93 (95% CI, 0.46-1.9) for VTE-BLEED to 1.67 (95% CI, 0.86-3.2) for ABC-Bleeding. Recalibration at 3-month follow-up did not alter the results., Conclusion: In this cohort, discrimination of currently available bleeding risk tools was poor. These data do not support their use in patients with unprovoked VTE., Competing Interests: Declaration of competing interests N.A.M.G., A.-M.L.B., S.S.W., N.K., F.I.M., M.J.L.P., M.t.W, J.M.M.B.O., E.P., V.S.-L., and P.M.M.B. have no competing interests to disclose. M.C. has received research funding from BMS, Pfizer, and LEO Pharma. He has also received Honoria from Bayer, BMS, Pfizer, Servier, and LEO Pharma. A.D. has received research funding from BMS-Pfizer and Honoria from Bayer, BMS-Pfizer, Servier, and LEO Pharma. L.J.-P. has received research funding from LEO Pharma and MSD. He has also received honoraria from Bayer Hispania, Actelion, Pfizer, Rovi, LEO Pharma, Menarini, and MSD. M.D. has received research funding from LEO Pharma and honoraria and consultancy fees from Daiichi Sankyo, Bayer, BMS-Pfizer, Sanofi, and LEO Pharma outside the submitted work. W.A. has received research funding from Bayer and honoraria from Bayer, BMS-Pfizer, Aspen, Sanofi, Janssen, Werfen, LEO Pharma, and Portola. J.B.-W. has received research funding from Bayer, Daiichi Sankyo, Pfizer, and Portola/Alexion. He has also received honoraria from Bayer, Daiichi Sankyo, Pfizer, and Portola/Alexion. T.V. has served as a speaker and/or advisor for Boehringer Ingelheim, Daiichi Sankyo, BMS/Pfizer, Bayer, Sanofi, and LEO Pharma. F.A.K. reports research grants from Bayer, Bristol-Myers Squibb, Boehringer Ingelheim, MSD, Daiichi Sankyo, Actelion, the Dutch Thrombosis Association, and the Dutch Heart foundation. B.C. reports speakers’ fees from Daiichi Sankyo and Sanofi. V.E.A.G. reports lecture fees from Novo Nordisk, and funding of studies by Dutch Thrombosis Foundation, AstraZeneca, and Zambon. H.B. reports consulting fees from Daiichi Sankyo, Bayer Healthcare, BMS/Pfizer, Boehringer Ingelheim, Portola, Medscape, Eli Lilly, Sanofi Aventis, and Ionis. N.v.E. has received advisory board honoraria from Daiichi Sankyo, Bayer, and LEO Pharma, which were transferred to his institute. P.W.K. received research grants from Daiichi Sankyo and Roche Diagnostics., (Copyright © 2024. Published by Elsevier Inc.)

Background and Aims: Home treatment is considered safe in acute pulmonary embolism (PE) patients selected by a validated triage tool (e.g. simplified PE severity index score or Hestia rule), but there is uncertainty regarding the applicability in underrepresented subgroups. The aim was to evaluate the safety of home treatment by performing an individual patient-level data meta-analysis., Methods: Ten prospective cohort studies or randomized controlled trials were identified in a systematic search, totalling 2694 PE patients treated at home (discharged within 24 h) and identified by a predefined triage tool. The 14- and 30-day incidences of all-cause mortality and adverse events (combined endpoint of recurrent venous thromboembolism, major bleeding, and/or all-cause mortality) were evaluated. The relative risk (RR) for 14- and 30-day mortalities and adverse events is calculated in subgroups using a random effects model., Results: The 14- and 30-day mortalities were 0.11% [95% confidence interval (CI) 0.0-0.24, I2 = 0) and 0.30% (95% CI 0.09-0.51, I2 = 0). The 14- and 30-day incidences of adverse events were 0.56% (95% CI 0.28-0.84, I2 = 0) and 1.2% (95% CI 0.79-1.6, I2 = 0). Cancer was associated with increased 30-day mortality [RR 4.9; 95% prediction interval (PI) 2.7-9.1; I2 = 0]. Pre-existing cardiopulmonary disease, abnormal troponin, and abnormal (N-terminal pro-)B-type natriuretic peptide [(NT-pro)BNP] at presentation were associated with an increased incidence of 14-day adverse events [RR 3.5 (95% PI 1.5-7.9, I2 = 0), 2.5 (95% PI 1.3-4.9, I2 = 0), and 3.9 (95% PI 1.6-9.8, I2 = 0), respectively], but not mortality. At 30 days, cancer, abnormal troponin, and abnormal (NT-pro)BNP were associated with an increased incidence of adverse events [RR 2.7 (95% PI 1.4-5.2, I2 = 0), 2.9 (95% PI 1.5-5.7, I2 = 0), and 3.3 (95% PI 1.6-7.1, I2 = 0), respectively]., Conclusions: The incidence of adverse events in home-treated PE patients, selected by a validated triage tool, was very low. Patients with cancer had a three- to five-fold higher incidence of adverse events and death. Patients with increased troponin or (NT-pro)BNP had a three-fold higher risk of adverse events, driven by recurrent venous thromboembolism and bleeding., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

The American College of Chest Physicians (CHEST) Antithrombotic Therapy for Venous Thromboembolism Disease evidence-based guidelines are now updated in a more frequent, focused manner. Guidance statements from the most recent full guidelines and two subsequent updates have not been gathered into a single source. An international panel of experts with experience in prior antithrombotic therapy guideline development reviewed the 2012 CHEST antithrombotic therapy guidelines and its two subsequent updates. All guideline statements and their associated patient, intervention, comparator, and outcome questions were assembled. A modified Delphi process was used to select statements considered relevant to current clinical care. The panel further endorsed minor phrasing changes to match the standard language for guidance statements using the modified Grading of Recommendations, Assessment, Development, and Evaluations (ie, GRADE) format endorsed by the CHEST Guidelines Oversight Committee. The panel appended comments after statements deemed as relevant, including suggesting that statements be updated in future guidelines because of interval evidence. We include 58 guidance statements from prior versions of the antithrombotic therapy guidelines, with updated phrasing as needed to adhere to contemporary nomenclature. Statements were classified as strong or weak recommendations based on high-certainty, moderate-certainty, and low-certainty evidence using GRADE methodology. The panel suggested that five statements are no longer relevant to current practice. As CHEST continues to update guidance statements relevant to antithrombotic therapy for VTE disease, this article serves as a unified collection of currenrtly relevant statements from the preceding three guidelines. Suggestions have been made to update specific statements in future publications., Competing Interests: Financial/Nonfinancial Disclosures The authors have reported to CHEST the following: L. B. K. reports receiving research funding from CSL Behring and Takeda to her institution for unrelated research. None declared S. M. S., S. C. W., K. D., G.-J. G., F. A. K., C. S. K., S. M., J. R. E. V., P. S. W., S. W., and L. K. M., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Introduction: Up to 50% of pulmonary embolism (PE) patients have perfusion defects or residual vascular obstruction during follow-up despite adequate anticoagulant treatment, and a similar percentage experience chronic functional limitations and/or dyspnoea post-PE. We aimed to evaluate the association between pulmonary perfusion defects or residual vascular obstruction and functional recovery after PE., Methods: We performed a systematic review and meta-analysis including studies assessing both the presence of perfusion defects or residual vascular obstruction and functional recovery ( i.e. persistent symptoms, quality of life, exercise endurance). An odds ratio was pooled for perfusion defects or residual vascular obstruction and persistent symptoms using a random-effect model., Results: 12 studies were included totalling 1888 PE patients; at a median of 6 months after PE (range 2-72 months), 34% had perfusion defects or residual vascular obstruction and 37% reported persistent symptoms. Among patients with perfusion defects or residual vascular obstruction, 48% (95% CI 37-60%, I 2 =82%) remained symptomatic during follow-up, compared to 34% (95% CI 20-51%, I 2 =96%) of patients without such defects. Presence of perfusion defects or residual vascular obstruction was associated with persistent symptoms (OR 2.15, 95% CI 1.66-2.78; I 2 =0%, τ = 0). Notably, there was no association between these defects and quality of life or cardiopulmonary exercise test parameters., Conclusion: While the odds of having persistent symptoms was higher in patients with perfusion defects or residual vascular obstruction after acute PE, a significant proportion of these patients reported no limitations. A possible causality between perfusion defects or residual vascular obstruction and residual functional limitation therefore remains to be proven., Competing Interests: Conflict of interest: W. Ghanima reports receiving fees for participation in advisory boards from Amgen, Novartis, Pfizer, Principia Biopharma Inc. (a Sanofi Company), Sanofi, SOBI, Grifols, UCB, Argenx, Cellphire, Alpine, Kedrion, HiBio and Hutchmed, outside the submitted work; lecture honoraria from Amgen, Novartis, Pfizer, Bristol Myers Squibb, SOBI, Grifols, Sanofi and Bayer, outside the submitted work; and research grants from Bayer, BMS/Pfizer and UCB, outside the submitted work. Conflict of interest: Y. Nakano received speaker and lecturer fees from Bayer, Daiichi-Sankyo, Janssen Pharmaceutical and Nippon Shinyaku, outside the submitted work. Conflict of interest: F.A. Klok has 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, outside the submitted work. Conflict of interest: The remaining authors have nothing to disclose., (Copyright ©The authors 2024.)

Background: Early thromboprophylaxis does not prevent hospital admissions and death among outpatients with symptomatic COVID-19. Its impact on long-term outcomes, including long COVID symptoms and performance status, is unknown., Objectives: To assess the long-term effects of thromboprophylaxis given at the time of acute COVID-19 in outpatients., Methods: The OVID (enoxaparin for outpatients with COVID-19) trial randomized outpatients older than 50 years with acute COVID-19 to receive either subcutaneous enoxaparin 40 mg once daily for 14 days or standard of care (no thromboprophylaxis). In this follow-up study, we assessed the 2-year outcomes, including all-cause hospitalization and death, cardiovascular events, long COVID symptoms, and functional limitations based on the Post-COVID-19 Functional Status (PCFS) scale and EuroQol-5 Dimensions-5 Levels scale., Results: Of 469 potentially eligible patients, 468 survived, of whom 439 (mean age 59 years; 54% men) participated in the Post-OVID study. There was no difference in terms of hospitalization and death (8.3% in the treatment group vs 10% in controls; relative risk, 0.83; 95% CI, 0.5-1.5) and of cardiovascular events between groups. The risk of presenting with long COVID symptoms was similar in the 2 groups (44% in the treatment group vs 47% in the standard of care group), with no difference between groups also concerning individual symptoms. A PCFS grade of 1 to 3, indicating light-to-moderate functional limitation, was recorded in 15% of patients in each group (odds ratio, 0.98; 95% CI, 0.6-1.7). No patients reported severe limitations (PCFS grade 4). Median EuroQol visual analog scale score was 85 on 100 points (IQR, 80-90 for the standard of care group and 75-90 for the enoxaparin group)., Conclusion: Early thromboprophylaxis does not improve long-term, 2-year clinical and functional outcomes among symptomatic ambulatory patients with acute COVID-19., (© 2024 The Author(s).)

Background  The noninvasive magnetic resonance direct thrombus imaging (MRDTI) technique can be used to diagnose acute deep vein thrombosis (DVT), without the use of intravenous contrast. MRDTI holds the potential to differentiate between acute and chronic DVT and could be helpful when diagnosing thrombosis is challenging. Objectives  Our objective was to evaluate the application of MRDTI in clinical practice, including the frequency and indications of MRDTI scans performed in practice-based conditions, results, impact on treatment decisions, and associated patient outcomes. Methods  A retrospective study was performed at the Leiden University Medical Center, the Netherlands. MRDTI scans performed since its implementation in patients aged ≥18 years as part of clinical practice for the diagnostic management of suspected thrombosis were evaluated. Results  Between October 2015 and September 2023, 36 patients had undergone MRDTI for the diagnostic evaluation of thrombosis. MRDTI application increased since 2019 (five-eight scans per year). The most common indication was to differentiate between acute and chronic thrombosis, mainly for suspected recurrent ipsilateral DVT after inconclusive compression ultrasonography. In over a third of patients, acute thrombosis was confirmed by MRDTI. MRDTI results determined treatment decisions in all except two patients. One patient had symptomatic thrombosis of the lower extremity within 3 months after an MRDTI of the upper extremity without signs of acute thrombosis (1/23; 4.3%, 95% confidence interval: 0.77-21). Conclusion  Over the past 4 years, MRDTI has been used increasingly in our hospital. MRDTI results guided treatment decisions, which confirms the clinical impact and feasibility of its application in daily practice., Competing Interests: Conflict of Interest F.A.K. reports grants or contracts from Bayer, BMS, BSCI, MSD, Leo Pharma, Actelion, VarmX, The Netherlands Organisation for Health Research and Development, The Dutch Thrombosis Association, The Dutch Heart Foundation and the Horizon Europe Program, all unrelated to this work and paid to his institution. H.C.J. Eikenboom reports research support from CSL Behring paid to the institute. C.M.M.J., L.F.D., C.E.A.D, P.L.E, S.N.M.H, G.R.H, M.V.H, T.E.M, J.L.S, L.J.M.K declare no conflict of interest., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. ( https://creativecommons.org/licenses/by/4.0/ ).)

Background and Aims: Coexisting atrial fibrillation (AF) and cancer challenge the management of both. The aim of the study is to comprehensively provide the epidemiology of coexisting AF and cancer., Methods: Using Dutch nationwide statistics, individuals with incident AF (n = 320 139) or cancer (n = 472 745) were identified during the period 2015-19. Dutch inhabitants without a history of AF (n = 320 135) or cancer (n = 472 741) were matched as control cohorts by demographic characteristics. Prevalence of cancer/AF at baseline, 1-year risk of cancer/AF diagnosis, and their time trends were determined. The association of cancer/AF diagnosis with all-cause mortality among those with AF/cancer was estimated by using time-dependent Cox regression., Results: The rate of prevalence of cancer in the AF cohort was 12.6% (increasing from 11.9% to 13.2%) compared with 5.6% in the controls; 1-year cancer risk was 2.5% (stable over years) compared with 1.8% in the controls [adjusted hazard ratio (aHR) 1.52, 95% confidence interval (CI) 1.46-1.58], which was similar by cancer type. The rate of prevalence of AF in the cancer cohort was 7.5% (increasing from 6.9% to 8.2%) compared with 4.3% in the controls; 1-year AF risk was 2.8% (stable over years) compared with 1.2% in the controls (aHR 2.78, 95% CI 2.69-2.87), but cancers of the oesophagus, lung, stomach, myeloma, and lymphoma were associated with higher hazards of AF than other cancer types. Both cancer diagnosed after incident AF (aHR 7.77, 95% CI 7.45-8.11) and AF diagnosed after incident cancer (aHR 2.55, 95% CI 2.47-2.63) were associated with all-cause mortality, but the strength of the association varied by cancer type., Conclusions: Atrial fibrillation and cancer were associated bidirectionally and were increasingly coexisting, but AF risk varied by cancer type. Coexisting AF and cancer were negatively associated with survival., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Objective: Patients surviving acute pulmonary embolism (PE) necessitate long-term treatment and follow-up. However, the chronic economic impact of PE on European healthcare systems remains to be determined., Methods and Results: We calculated the direct cost of illness during the first year after discharge for the index PE, analyzing data from a multicentre prospective cohort study in Germany. Main and accompanying readmission diagnoses were used to calculate DRG-based hospital reimbursements; anticoagulation costs were estimated from the exact treatment duration and each drug's unique national identifier; and outpatient post-PE care costs from guidelines-recommended algorithms and national reimbursement catalogues. Of 1017 patients enrolled at 17 centres, 958 (94%) completed ≥ 3-month follow-up; of those, 24% were rehospitalized (0.34 [95% CI 0.30-0.39] readmissions per PE survivor). Age, coronary artery, pulmonary and kidney disease, diabetes, and (in the sensitivity analysis of 837 patients with complete 12-month follow-up) cancer, but not recurrent PE, were independent cost predictors by hurdle gamma regression accounting for zero readmissions. Estimated rehospitalization cost was €1138 (95% CI 896-1420) per patient. Anticoagulation duration was 329 (IQR 142-365) days, with estimated average per-patient costs of €1050 (median 972; IQR 458-1197); costs of scheduled ambulatory follow-up visits amounted to €181. Total estimated direct per-patient costs during the first year after PE ranged from €2369 (primary analysis) to €2542 (sensitivity analysis)., Conclusions: By estimating per-patient costs and identifying cost drivers of post-PE care, our study may inform decisions concerning implementation and reimbursement of follow-up programmes aiming at improved cardiovascular prevention. (Trial registration number: DRKS00005939)., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

An accurate and prompt diagnosis of deep vein thrombosis and/or pulmonary embolism is important to prevent serious complications and mortality. Because the clinical presentation of venous thromboembolism (VTE) is often nonspecific, objective testing by means of radiological imaging is required to confirm the diagnosis. Historically, a diagnosis of VTE involved invasive imaging techniques like contrast venography or conventional pulmonary angiography. Technological developments toward more accurate and less invasive diagnostics have driven the implementation of a variety of newer technologies over the past decades, as well as the derivation and validation of clinical decision rules (CDRs) that can be used to rule out VTE in combination with D-dimer blood tests. In this narrative review, we provide a historical overview of the most notable developments in the imaging techniques and CDRs for VTE diagnosis., Competing Interests: None declared., (Thieme. All rights reserved.)

Background: Due to the rarity of cerebral venous thrombosis (CVT), performing high-quality scientific research in this field is challenging. Providing answers to unresolved research questions will improve prevention, diagnosis, and treatment, and ultimately translate to a better outcome of patients with CVT. We present an international research agenda, in which the most important research questions in the field of CVT are prioritized., Aims: This research agenda has three distinct goals: (1) to provide inspiration and focus to research on CVT for the coming years, (2) to reinforce international collaboration, and (3) to facilitate the acquisition of research funding., Summary of Review: This international research agenda is the result of a research summit organized by the International Cerebral Venous Thrombosis Consortium in Amsterdam, the Netherlands, in June 2023. The summit brought together 45 participants from 15 countries including clinical researchers from various disciplines, patients who previously suffered from CVT, and delegates from industry and non-profit funding organizations. The research agenda is categorized into six pre-specified themes: (1) epidemiology and clinical features, (2) life after CVT, (3) neuroimaging and diagnosis, (4) pathophysiology, (5) medical treatment, and (6) endovascular treatment. For each theme, we present two to four research questions, followed by a brief substantiation per question. The research questions were prioritized by the participants of the summit through consensus discussion., Conclusions: This international research agenda provides an overview of the most burning research questions on CVT. Answering these questions will advance our understanding and management of CVT, which will ultimately lead to improved outcomes for CVT patients worldwide., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: J.M.C. has received research support paid to his institution from Boehringer Ingelheim, Bayer, and Astra Zeneca. J.M.C. is co-founder and shareholder of TrianecT; D.A.d.S. reported personal fees for Astra Zeneca, Organon, Daiichi Sankyo and Johnson & Johnson advisory board participation, DSMB participation for the SECRET trial (University of British Columbia), and speaking fees from Bayer and Bial; S.P. has received research support from BMS/Pfizer, Boehringer Ingelheim, Daiichi Sankyo, European Union, German Federal Joint Committee Innovation Fund, German Federal Ministry of Education and Research, Helena Laboratories, and Werfen as well as speakers’ honoraria/consulting fees from Alexion, Astra Zeneca, Bayer, Boehringer Ingelheim, BMS/Pfizer, Daiichi Sankyo, Portola, and Werfen; A.A. has received research support paid to his Institution from Astra Zeneca; M.S.v.K. has received research support from the Amstol foundation; R.v.d.B. has received research support paid to his institution from CERENOVUS; T.S.F. has received in-kind study medication from Bayer Canada and has received personal fees from Bayer Canada and Roche for advosiry board participation; M.R.H. has received grants from the Swiss National Science Foundation, the SITEM Research Funds, and the Swiss Heart Foundation, all outside the submitted work; M.H.-P. has received compensation for scientific research by AptaTargets; F.A.K. has received research support from Bayer, BMS, BSCI, Astra Zeneca, MSD, Leo Pharma, Actelion, Farm-X, The Netherlands Organization for Health Research and Development, The Dutch Thrombosis Foundation, The Dutch Heart Foundation, and the Horizon Europe Program; R.R.L. has received speaker honoraria from IscemaView, Boehringer Ingelheim, Pfizer, Jansen, Biogen, Medtronic, and Abott and advisory board honoraria from Jansen, Bayer, and Filterlex; T.N.N. has disclosed advisory board for Idorsia and Brainomix; G.S. has received a stipend as the Editor-in-Chief of the World Stroke Academy for the World Stroke Organization; V.T. has received speaker honoraria from Boehringer Ingelheim and Bayer & Astra Zeneca and is on the steering committee of the Librexia Stroke trial, sponsored by Johnson & Johnson; D.J.W. has received grant funding from the Stroke Association and British Heart Foundation, speaking honoraria from Bayer, speaking and chairing honoraria from Alexion and NovoNordisk, and consultancy fees from Alnylam, Bayer, and NovoNordisk; T.T. has served/serves on scientific advisory boards for Astra Zeneca, Argenx, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Inventiva, and Portola Pharm and has received academic funding from University of Gothenburg, Sahlgrenska University Hospital, European Union, Sigrid Juselius Foundation, and Wennerström’s Foundation. The other authors have nothing to disclose.

The first-choice imaging test for visualization of thromboemboli in the pulmonary vasculature in patients with suspected acute pulmonary embolism (PE) is multidetector computed tomography pulmonary angiography (CTPA) - a readily available and widely used imaging technique. Through technological advancements over the past years, alternative imaging techniques for the diagnosis of PE have become available, whilst others are still under investigation. In particular, the evolution of artificial intelligence (AI) is expected to enable further innovation in diagnostic management of PE. In this narrative review, current CTPA techniques and the emerging technology photon-counting CT (PCCT), as well as other modern imaging techniques of acute PE are discussed, including CTPA with iodine maps based on subtraction or dual-energy acquisition, single-photon emission CT (SPECT), magnetic resonance angiography (MRA), and magnetic resonance direct thrombus imaging (MRDTI). Furthermore, potential applications of AI are discussed., Competing Interests: Declaration of competing interest C.M.M. de Jong reports no conflict of interest. L.J.M. Kroft reports no conflict of interest. T.E. van Mens reports no conflict of interest. M.V. Huisman reports no conflict of interest. J.L. Stöger reports no conflict of interest. F.A. Klok reports grants or contracts from Bayer, BMS, BSCI, MSD, Leo Pharma, Actelion, VarmX, The Netherlands Organization for Health Research and Development, The Dutch Thrombosis Association, The Dutch Heart Foundation and the Horizon Europe Program, all unrelated to this work and paid to his institution., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background:  The diagnosis of recurrent ipsilateral deep vein thrombosis (DVT) with compression ultrasonography (CUS) may be hindered by residual intravascular obstruction after previous DVT. A reference CUS, an additional ultrasound performed at anticoagulant discontinuation, may improve the diagnostic work-up of suspected recurrent ipsilateral DVT by providing baseline images for future comparison., Objectives:  To evaluate the cost-effectiveness of routinely performing reference CUS in DVT patients., Methods:  Patient-level data ( n  = 96) from a prospective management study (Theia study; NCT02262052) and claims data were used in a decision analytic model to compare 12 scenarios for diagnostic management of suspected recurrent ipsilateral DVT. Estimated health care costs and mortality due to misdiagnosis, recurrent venous thromboembolism, and bleeding during the first year of follow-up after presentation with suspected recurrence were compared., Results:  All six scenarios including reference CUS had higher estimated 1-year costs (€1,763-€1,913) than the six without reference CUS (€1,192-€1,474). Costs were higher because reference CUS results often remained unused, as 20% of patients (according to claims data) would return with suspected recurrent DVT. Estimated mortality was comparable in scenarios with (14.8-17.9 per 10,000 patients) and without reference CUS (14.0-18.5 per 10,000). None of the four potentially most desirable scenarios included reference CUS., Conclusion:  One-year health care costs of diagnostic strategies for suspected recurrent ipsilateral DVT including reference CUS are higher compared to strategies without reference CUS, without mortality benefit. These results can inform policy-makers regarding use of health care resources during follow-up after DVT. From a cost-effectiveness perspective, the findings do not support the routine application of reference CUS., Competing Interests: F.A.K. reports grants or contracts from Bayer, BMS, BSCI, MSD, Leo Pharma, Actelion, VarmX, The Netherlands Organisation for Health Research and Development, The Dutch Thrombosis Association, The Dutch Heart Foundation, and The Horizon Europe Program, all unrelated to this work and paid to his institution. All other authors report no conflict of interest., (Thieme. All rights reserved.)

Background: Venous thromboembolism (VTE) is associated with various long-term complications., Objectives: We aimed to investigate the association of clinical characteristics at VTE diagnosis with functional limitations 3 and 12 months afterward., Methods: We conducted a prospective cohort study of VTE patients, excluding patients with cancer, pregnancy, and postpartum period. Functional limitations were assessed with the post-VTE functional status (PVFS) scale (range, 0-4) within 21 days of diagnosis, after 3 and 12 months (prospectively), and 1 month before diagnosis (retrospectively). Twelve-month follow-up was only performed in patients on anticoagulation. We fitted 2 proportional odds logistic regression models for the 3- and 12-month follow-ups and computed odds ratios (ORs) with 95% bootstrap percentile confidence intervals (CIs)., Results: We included 307 patients (42% female, median age 55.6 years) with a median (IQR) PVFS scale grade of 2 (2-3) at study inclusion and 0 (0-0) before diagnosis. After 3 months, PVFS scale grade in 269 patients was 1 (0-2). Female sex (OR, 2.15; 95% CI, 1.26-4.14), body mass index (OR per 1 kg/m 2 increase, 1.05; 95% CI, 1.00-1.10), functional limitations at baseline, and older age were associated with functional limitations. After 12 months, PVFS scale grade in 124 patients was 1 (0-2). Female sex (OR, 4.47; 95% CI, 2.11-16.00), history of cardiovascular/pulmonary disease (OR, 2.36; 95% CI, 1.01-6.89), and functional limitations at baseline were associated with functional limitations., Conclusion: Functional limitations in VTE patients improved 3 and 12 months after diagnosis but did not return to pre-VTE values. We identified clinical characteristics that could help identify patients at risk of persisting functional limitations after VTE., (© 2024 The Author(s).)

Background: Patients with Cushing syndrome (CS) are at increased risk of venous thromboembolism (VTE)., Objective: The aim was to evaluate the current management of new cases of CS with a focus on VTE and thromboprophylaxis., Design and Methods: A survey was conducted within those that report in the electronic reporting tool (e-REC) of the European Registries for Rare Endocrine Conditions (EuRRECa) and the involved main thematic groups (MTG's) of the European Reference Networks for Rare Endocrine Disorders (Endo-ERN) on new patients with CS from January 2021 to July 2022., Results: Of 222 patients (mean age 44 years, 165 females), 141 patients had Cushing disease (64%), 69 adrenal CS (31%), and 12 patients with ectopic CS (5.4%). The mean follow-up period post-CS diagnosis was 15 months (range 3-30). Cortisol-lowering medications were initiated in 38% of patients. One hundred fifty-four patients (69%) received thromboprophylaxis (including patients on chronic anticoagulant treatment), of which low-molecular-weight heparins were used in 96% of cases. VTE was reported in six patients (2.7%), of which one was fatal: two long before CS diagnosis, two between diagnosis and surgery, and two postoperatively. Three patients were using thromboprophylaxis at time of the VTE diagnosis. The incidence rate of VTE in patients after Cushing syndrome diagnosis in our study cohort was 14.6 (95% CI 5.5; 38.6) per 1000 person-years., Conclusion: Thirty percent of patients with CS did not receive preoperative thromboprophylaxis during their active disease stage, and half of the VTE cases even occurred during this stage despite thromboprophylaxis. Prospective trials to establish the optimal thromboprophylaxis strategy in CS patients are highly needed., Significance Statement: The incidence rate of venous thromboembolism in our study cohort was 14.6 (95% CI 5.5; 38.6) per 1000 person-years. Notably, this survey showed that there is great heterogeneity regarding time of initiation and duration of thromboprophylaxis in expert centers throughout Europe.

Background: Implantation of a left ventricular assist device (LVAD) is a crucial therapeutic option for selected end-stage heart failure patients. However, major bleeding (MB) complications postimplantation are a significant concern., Objectives: We evaluated current risk scores' predictive accuracy for MB in LVAD recipients., Methods: We conducted an observational, single-center study of LVAD recipients (HeartWare or HeartMate-3, November 2010-December 2022) in the Netherlands. The primary outcome was the first post-LVAD MB (according to the International Society on Thrombosis and Haemostasis [ISTH] and Interagency Registry for Mechanically Assisted Circulatory Support [INTERMACS], and INTERMACS combined with intracranial bleeding [INTERMACS+] criteria). Mortality prior to MB was considered a competing event. Discrimination (C-statistic) and calibration were evaluated for the Hypertension, Abnormal Renal/Liver Function, Stroke, Bleeding History or Predisposition, Labile INR, Elderly, Drugs/Alcohol Concomitantly score, Hepatic or Renal Disease, Ethanol Abuse, Malignancy, Older Age, Reduced Platelet Count or Function, Re-Bleeding, Hypertension, Anemia, Genetic Factors, Excessive Fall Risk and Stroke score, Anticoagulation and Risk Factors in Atrial Fibrillation score, Outpatient Bleeding Risk Index, venous thromboembolism score, atrial fibrillation score, and Utah Bleeding Risk Score (UBRS)., Results: One hundred four patients were included (median age, 64 years; female, 20.2%; HeartWare, 90.4%; HeartMate-3, 9.6%). The cumulative MB incidence was 75.7% (95% CI 65.5%-85.9%) by ISTH and INTERMACS+ criteria and 67.0% (95% CI 56.0%-78.0%) per INTERMACS criteria over a median event-free follow-up time of 1916 days (range, 59-4521). All scores had poor discriminative ability on their intended prediction timeframe. Cumulative area under the receiving operator characteristic curve ranged from 0.49 (95% CI 0.35-0.63, venous thromboembolism-BLEED) to 0.56 (95% CI 0.47-0.65, UBRS) according to ISTH and INTERMACS+ criteria and from 0.48 (95% CI 0.40-0.56, Anticoagulation and Risk Factors in Atrial Fibrillation) to 0.56 (95% CI 0.47-0.65, UBRS) per INTERMACS criteria. All models showed poor calibration, largely underestimating MB risk., Conclusion: Current bleeding risk scores exhibit inadequate predictive accuracy for LVAD recipients. There is a need for an accurate risk score to identify LVAD patients at high risk of MB who may benefit from patient-tailored antithrombotic therapy., (© 2024 The Author(s).)

Pulmonary embolism (PE) is a common disease, which can present with a variety of symptoms. Optimal use of diagnostics is challenging given the tight and delicate balance between underdiagnosis and over-testing or overdiagnosis. Diagnostic delay occurs in a substantial part of patients, and seems more common in those with known cardiopulmonary disease or non-specific signs and symptoms. At the other end of the spectrum, the amount of diagnostic imaging increases. Increased use of diagnostic imaging in general leads to more harmful exposures and might result in overtreatment, as may be the case in subsegmental PE. Correct use of clinical prediction rules reduces the need for diagnostic imaging while PE can still be ruled out safely. This clinical lesson describes three cases of PE and provides an overview of factors that contribute to underdiagnosis or overdiagnosis. We provide recommendations to improve our balancing act for this challenging disease.

Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare form of pulmonary hypertension characterized by the presence of organized thrombi that obstruct pulmonary arteries, ultimately leading to right heart failure and death. Among others, impaired angiogenesis and inflammatory thrombosis have been shown to contribute to the progression of CTEPH. In this review, we summarize the 2-faced nature of angiogenesis in both thrombus formation and resolution in the context of CTEPH and highlight the dual role of angiogenesis and neovascularization in resolving venous thrombi. Furthermore, we discuss relevant in vitro and in vivo models that support the benefits or drawbacks of angiogenesis in CTEPH progression. We discuss the key pathways involved in modulating angiogenesis, particularly the underexplored role of TGFβ (transforming growth factor-beta) signaling in driving fibrosis as an integral element of CTEPH pathogenesis. We finally explore innovative treatment strategies that target angiogenic pathways. These strategies have the potential to pioneer preventive, inventive, or alternative therapeutic options for patients with CTEPH who may not qualify for surgical interventions. Moreover, they could be used synergistically with established treatments such as pulmonary endarterectomy or balloon pulmonary angioplasty. In summary, this review emphasizes the crucial role of angiogenesis in the development of in fibrothrombotic tissue, a major pathological characteristic of CTEPH., Competing Interests: Disclosures M. Delcroix received financial support from the Belgian Pulmonary Hypertension Patient Association. The other authors report no conflicts.

Background: Treatment guidelines for splanchnic vein thrombosis in necrotizing pancreatitis are lacking due to insufficient data on the full clinical spectrum., Methods: We performed a post-hoc analysis of a nationwide prospective necrotizing pancreatitis cohort. Multivariable analyses were used to identify risk factors and compare the clinical course of patients with and without SVT., Results: SVT was detected in 97 of the 432 included patients (22%) (median onset: 4 days). Risk factors were left, central, or subtotal necrosis (OR 28.52; 95% CI 20.11-40.45), right or diffuse necrosis (OR 5.76; 95% CI 3.89-8.51), and younger age (OR 0.94; 95% CI 0.90-0.97). Patients with SVT had higher rates of bleeding (n = 10,11%) and bowel ischemia (n = 4,4%) compared to patients without SVT (n = 14,4% and n = 2,0.6%; OR 3.24; 95% CI 1.27-8.23 and OR 7.29; 95% CI 1.31-40.4, respectively), and were independently associated with ICU admission (adjusted OR 2.53; 95% CI 1.37-4.68). Spontaneous recanalization occurred in 62% of patients (n = 40/71). Radiological and clinical outcomes did not differ between patients treated with and without anticoagulants., Discussion: SVT is a common and early complication of necrotizing pancreatitis, associated with parenchymal necrosis and younger age. SVT is associated with increased complications and a worse clinical course, whereas anticoagulant use does not appear to affect outcomes., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Introduction: Patients with a first venous thromboembolism (VTE) are at risk of recurrence. Recurrent VTE (rVTE) can be prevented by extended anticoagulant therapy, but this comes at the cost of an increased risk of bleeding. It is still uncertain whether patients with an intermediate recurrence risk or with a high recurrence and high bleeding risk will benefit from extended anticoagulant treatment, and whether a strategy where anticoagulant duration is tailored on the predicted risks of rVTE and bleeding can improve outcomes. The aim of the Leiden Thrombosis Recurrence Risk Prevention (L-TRRiP) study is to evaluate the outcomes of tailored duration of long-term anticoagulant treatment based on individualised assessment of rVTE and major bleeding risks., Methods and Analysis: The L-TRRiP study is a multicentre, open-label, cohort-based, randomised controlled trial, including patients with a first VTE. We classify the risk of rVTE and major bleeding using the L-TRRiP and VTE-BLEED scores, respectively. After 3 months of anticoagulant therapy, patients with a low rVTE risk will discontinue anticoagulant treatment, patients with a high rVTE and low bleeding risk will continue anticoagulant treatment, whereas all other patients will be randomised to continue or discontinue anticoagulant treatment. All patients will be followed up for at least 2 years. Inclusion will continue until the randomised group consists of 608 patients; we estimate to include 1600 patients in total. The primary outcome is the combined incidence of rVTE and major bleeding in the randomised group after 2 years of follow-up. Secondary outcomes include the incidence of rVTE and major bleeding, functional outcomes, quality of life and cost-effectiveness in all patients., Ethics and Dissemination: The protocol was approved by the Medical Research Ethics Committee Leiden-Den Haag-Delft. Results are expected in 2028 and will be disseminated through peer-reviewed journals and during (inter)national conferences., Trial Registration Number: NCT06087952., Competing Interests: Competing interests: MC has received financial support for research from Bayer, CSL Behring, Roche, Novo Nordisk and UniQure and lees for lecturing or consultancy from Alexion, Bayer, CSL Behring, Daiichi Sankyo, Sobi and Viatris, all unrelated to the present work and paid to his institution. NvE has received a lecture fee from Bristol Myers Squibb, which was unrelated to this work and paid to his institution. JL reports grants or contracts from BMS-Pfizer, Viatris, AstraZeneca and Synapse, all unrelated to this work and paid to her institution. KM reports speaker fees from Alexion, Bayer and CSL Behring, participation in trial steering committees for Bayer and AstraZeneca, consulting fees from Uniqure, participation in data monitoring and endpoint adjudication committee for Octapharma. All payments are made to her institution. SM reports grants and personal fees from Daiichi-Sankyo, Bayer, Pfizer and Boehringer-Ingelheim, personal fees from Portola/Alexion, AbbVie, Pfizer/Bristol-Meyers Squibb, Norgine, Viatris and Sanofi, all paid to her institution and outside the submitted work. MVH reports grants from Dutch Heart Foundation, Netherlands Organisation for Health Research and Development, Bayer Health Care, Pfizer-BMS Leo Pharma Boehringer-Ingelheim, all outside this work. FAK reports grants or contracts from Bayer, BMS, BSCI, MSD, Leo Pharma, Actelion, Farm-X, The Netherlands Organisation for Health Research and Development, the Dutch Thrombosis Association, The Dutch Heart Foundation and the Horizon Europe Program, all unrelated to this work and paid to his institution. All others report no conflicts of interest related to this project., (© 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: Up to 50 % of patients surviving a pulmonary embolism (PE) report persisting shortness of breath, reduced physical capacity and psychological distress. As the PE population is heterogeneous compared to other cardiovascular patient groups, outcome measures for assessing physical capacity traditionally used in cardiac populations may not be reliable for the PE population as a whole. This scoping review aims to 1) map performance-based outcome measures (PBOMs) used for assessing physical capacity in PE research, and 2) to report the psychometric properties of the identified PBOMs in a PE population., Methods: The review was conducted according to the Joanna Briggs Institute framework for scoping reviews and reported according to the PRISMA-Extension for Scoping Reviews guideline., Results: The systematic search of five databases identified 4585 studies, of which 243 studies met the inclusion criteria. Of these, 185 studies focused on a subgroup of patients with chronic thromboembolic pulmonary hypertension. Ten different PBOMs were identified in the included studies. The 6-minute walk test (6MWT) and cardiopulmonary exercise test (CPET) were the most commonly used, followed by the (Modified) Bruce protocol and Incremental Shuttle Walk test. No studies reported psychometric properties of any of the identified PBOMs in a PE population., Conclusions: Publication of studies measuring physical capacity within PE populations has increased significantly over the past 5-10 years. Still, not one study was identified, reporting the validity, reliability, or responsiveness for any of the identified PBOMs in a PE population. This should be a priority for future research in the field., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: None related to this manuscript. The authors report the following general conflicts: ELG has received speaker honoraria or consultancy fees from AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Pfizer, Lundbeck Pharma, Novo Nordisk and Organon. He is investigator in clinical studies sponsored by AstraZeneca, Idorsia or Bayer and has received unrestricted research grants from Boehringer Ingelheim. AAH has received consulting fees from Bayer and The Bristol-Myers Squibb-Pfizer Alliance, and speaker bureaus from Bayer, The Bristol-Myers Squibb-Pfizer Alliance. NR has received speaker honoraria for talks about PE and rehabilitation and consultancy fees for the development of patient information material on the same subject, both sponsored by Bayer and Bristol-Myers Squibb-Pfizer Alliance., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)