Introduction Pulmonary embolism (PE) can result in long-term sequelae, such as the post-PE syndrome or chronic thromboembolic pulmonary hypertension (CTEPH) in survivors. The underlying factors contributing to cardiac and functional decline in affected patients remain unclear, and existing tools for identifying high-risk patients are insufficiently sensitive and specific. This study aimed to develop a machine learning model to identify patients at risk for long-term consequences, potentially improving diagnosis and understanding of post-PE syndrome.

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

and upon external validation in an independent cohort, these biomarker candidates may be incorporated in risk models to improve CAT prediction that might help identifying cancer patients who benefit most from thromboprophylaxis.

The publisher regrets that this article has been temporarily removed. A replacement will appear as soon as possible in which the reason for the removal of the article will be specified, or the article will be reinstated. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy.

Introduction: The aim was to analyze the clinical and prognostic differences between patients with PE with home and hospital treatment. Methods: The RIETE registry included 18145 and 1166 PE patients treated at hospital and at home. The clinical features were compared according to the treatment regimen. Results: Patients with home therapy were younger than patients treated at hospital (59.0±16.4 vs 66.8±17.2 years, p<0.001), presented less immobilization (15% vs 19%, OR 0.75, 95%CI 0.64-0.88) and had less unprovoked PE (50% vs 55%, OR 0.80, 95%CI 0.71-0.90), had more subsegmental PE (17% vs 4.6%, OR 4.17, 95%CI 3.42-5.09) and less proximal PE (16% vs 43%), OR 0.26, 95%CI 0.21-0.31), and had less heart affectation (7.6% vs 19%, OR 0.36, 95%CI 0.21-0.62). More proportion of patients without admission had PESI<65 (36% vs 19%, OR 2.45, 95%CI 2.16-2.78). At 7 days, patients treated at home presented less major bleeding (0.1% vs 0.8%, OR 0.11, 95%CI 0.02-0.78), less mortality (0.1% vs 1.6%, OR 0.05, 95%CI 0.01-0.38) and less event composed by recurrent PE, major bleeding and death (0.3% vs 2.4%, OR 0.14, 95%CI 0.05-0.38). Risk factors for the composite event were history of myocardial infarction (HR 1.38, 95%CI 1.01-1.90), chronic heart failure (HR 1.51, 95%CI 1.12-2.04), recent bleeding (HR 2.16, 95%CI 1.35-3.44), active cancer (HR 1.47, 95%CI 1.13-1.92), having transient risk factors (HR 1.67, 95%CI 1.33-2.11) and hospital admission (HR 4.24, 95%CI 1.56-11.57). Conclusion: PE patients treated at home were younger, less severe and less complicated than patients treated at hospital. Risk factors for the composite event were heart disease, bleeding, cancer and hospital admission.

The publisher regrets that this article has been temporarily removed. A replacement will appear as soon as possible in which the reason for the removal of the article will be specified, or the article will be reinstated. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy.

L’incidence de la maladie veineuse thromboembolique associée au cancer est en augmentation. Les essais thérapeutiques ont permis d’évaluer les HBPM par rapport aux AVK et plus récemment les AOD par rapport aux HBPM dans cette population. Le rapport bénéfice/risque du traitement pourrait être différent sur le site du cancer. Évaluer le risque de récidive thromboembolique veineuse, de saignement majeur et de décès à 12 mois chez les patients avec cancer du sein, de la prostate, et colorectal qui ont eu un ETEV et qui reçoivent une anticoagulation depuis au moins 3 mois. RIETE (Registro Informatizado Enfermedad TromboEmbolica) est un registre prospectif international observationnel créé en 2001, recueillant des données consécutives observationnelles de patients chez qui est diagnostiqué un événement thromboembolique veineux. Le risque de récidive thromboembolique veineux diffère selon le site de cancer ; il est plus élevé dans les 3 premiers mois (1,9 %, 1,7 %, et 2,9 %, pour le cancer du sein, de la prostate et colorectal, respectivement) qu’entre le 3e et le 12e mois (1,0 %, 1,9 %, et 1,9 % respectivement). En l’absence d’essai thérapeutique dédié, l’analyse du registre RIETE a permis de produire des données étayant l’hypothèse d’un rapport bénéfice/risque du traitement anticoagulant différent selon le site de cancer. Elles ont en particulier permis de construire l’étude APICAT évaluant une dose réduite d’anticoagulant selon le site de cancer chez les patients ayant reçu au moins 6 mois de traitement pour un événement thromboembolique veineux.

Background Many works aimed to determine factors that influence the onset of postthrombotic syndrome after an acute episode of deep venous thrombosis. We aimed to compare the prognostic value of the most proximal extent of thrombus (proximal and distal DVT) versus the residual thrombosis as identified by venous ultrasonography performed during follow-up. Method We conducted a retrospective study of prospectively collected 1183 consecutive cohort patients in the RIETE registry after a first episode of deep venous thrombosis and assessed for postthrombotic syndrome after 12 months. Results Multivariate analysis revealed that: residual thrombosis (OR 1.40; 95% CI 0,88-2,21), the presence of cancer (OR 1.38; 95% CI: 0,64-2,97), immobility (OR 1.31; 95% CI 0,70-2,43) and estrogen-containing drugs use (OR 2.08, 95% CI 0,63-6,83), all had a predictive value for the occurrence of PTS. Conclusion Our study results revealed that ultrasound finding of residual thrombosis is more predictive than proximal location of thrombus for postthrombotic syndrome after episode of deep venous thrombosis. Real life data from a large group of patients from the RIETE registry substantiates that.

ImportanceActive search for pulmonary embolism (PE) may improve outcomes in patients hospitalized for exacerbations of chronic obstructive pulmonary disease (COPD).ObjectiveTo compare usual care plus an active strategy for diagnosing PE with usual care alone in patients hospitalized for COPD exacerbation.Design, Setting, and ParticipantsRandomized 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).InterventionsUsual 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 MeasuresThe 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.ResultsAmong 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 RelevanceAmong 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 RegistrationClinicalTrials.gov Identifier: NCT02238639.

INTRODUCTION:An increased risk of ischemic stroke in patients with acute pulmonary embolism (PE) and patent foramen ovale (PFO) was reported but few data exist regarding prognostic outcomes of those patients.MATERIAL AND METHODS:Using data in the RIETE registry, we compared the characteristics, therapeutic approaches and outcomes of patients with PE according to the presence or absence of PFO.RESULTS:From August 2016 to January 2020, 4148 patients with acute PE were enrolled. Of these, 2775 (67%) had no transthoracic echocardiogram (TTE), 993 (24%) underwent TTE but had no reported results on PFO. Among the remaining 380 patients, 287 (74%) did not have PFO and 93 (26%) had PFO. Patients with PFO were more likely to have chronic heart failure, prior myocardial infarction or ischemic stroke than those without PFO. Patients with PFO had a higher rate of subsequent ischemic stroke than those without PFO (hazard ratio (HR): 9.28; 95% CI: 1.83-69.1), than those with TTE but no data on PFO (HR: 10.1; 95% CI: 2.56-42.4) or without TTE (HR: 9.78; 95% CI: 3.02-28.4). On multivariable analysis, patients with PFO were at increased risk for subsequent ischemic stroke than those without PFO (HR: 8.96; 95% CI: 1.68-47.7).CONCLUSIONS:PFO was searched in a minority of patients with an acute PE in real life setting. Subject to possible selection and measurement biases, our results confirmed a higher risk of ischemic stroke in PE patients with PFO compared to those without PFO. This association warrants further investigation before determining the best therapeutic option in patients with acute PE and concomitant PFO.

There is a lack of knowledge with regards to contemporary presentation, management, and outcomes of patients with venous thromboembolism (VTE). Many clinically important subgroups (including the elderly, those with recent bleeding, and pregnant patients) have been under-represented in clinical trials. Further, design of clinical trials is challenging in some scenarios, such as in those with hemodynamically unstable pulmonary embolism (PE). Registro Informatizado Enfermedad TromboEmbolica (RIETE) is a large prospective multinational ongoing registry, designed to address these unmet needs using representative data from multiple centres. Initiated in Spain in 2001, RIETE currently includes 206 centres in 28 countries and has enrolled over 87,000 patients with VTE. The overarching goal is to improve the management of VTE through better understanding of prevention, as well as demographics, co-morbidities, treatment patterns, and outcomes of patients with VTE. RIETE has helped characterise the pattern of presentation and outcomes of VTE, including in the aforementioned understudied subgroups, in over 150 research articles. RIETE has recently expanded to collect long-term outcomes data, and has broadened its inclusion criteria to enrol other forms of venous thrombosis (such as cerebral vein thrombosis and splanchnic vein thrombosis). The RIETE platform is also being used to conduct pragmatic comparative effectiveness studies, including randomised trials. Future steps would focus on collaboration with additional centres across the world, and efforts to ensure the quality and expansion of the registry. It is expected that RIETE will continue to provide clinical evidence for understudied subgroups with VTE, and will have more prominent role for facilitation of multicenter (and multinational studies) that could be used for assessment of variations and disparities in care, quality improvement, and conducting comparative effectiveness research. RIETE is a large ongoing registry of patients with VTE and other thrombotic conditions. Its results could be helpful for improving our understanding of the epidemiology, patterns of care and outcomes of patients with thrombotic disease.

Il y a un manque de connaissances en ce qui concerne la présentation, la prise en charge et le devenir des patients présentant une maladie thromboembolique veineuse (MTEV). De nombreux sous-groupes cliniquement pertinents (comme les personnes âgées, les hémorragies récentes et les patientes enceintes) ont été sous-représentés dans les essais cliniques. En outre, le design des essais cliniques est intéressant dans certains scénarios, comme par exemple ceux présentant une embolie pulmonaire (EP) hémodynamiquement instable. Registro Informatizado Enfermedad TromboEmbolica (RIETE) est un grand registre prospectif et international en cours, conçu pour répondre à ces besoins non satisfaits en utilisant des données représentatives de plusieurs centres. Créé en Espagne en 2001, RIETE comprend actuellement 206 centres répartis dans 28 pays et a recruté plus de 87 000 patients atteints de MTEV. L'objectif principal est d'améliorer la prise en charge de la MTEV grâce à une meilleure compréhension de la prévention, ainsi que des données démographiques, des comorbidités, des schémas de traitement et du devenir des patients atteints de MTEV. RIETE a contribué à caractériser le modèle de présentation et de devenir de la MTEV, y compris dans les sous-groupes peu étudiés mentionnés précédemment, dans plus de 150 articles de recherche. RIETE a récemment étendu ses activités à la collecte de données sur le devenir à long terme et a élargi ses critères d'inclusion pour inclure d'autres formes de thrombose veineuse (telles que la thrombose veineuse cérébrale et la thrombose veineuse splanchnique). La plateforme RIETE est également utilisée pour mener des études comparatives pragmatiques d'efficacité, notamment des essais randomisés. Les prochaines étapes seraient axées sur la collaboration avec d'autres centres dans le monde et sur les efforts visant à assurer la qualité et l'extension du registre. RIETE devrait continuer à fournir des preuves cliniques pour les sous-groupes de MTEV sous-étudiés et jouer un rôle plus important dans la facilitation d'études multicentriques (et internationales) pouvant être utilisées pour évaluer les variations et les disparités des soins, l'amélioration de la qualité et conduire des études comparatives d'efficacité. RIETE est un vaste registre, en cours, de patients atteints de MTEV et d'autres affections thrombotiques. Ses résultats pourraient être utiles pour améliorer notre compréhension de l'épidémiologie, des tendances en matière de soins et du devenir des patients atteints de maladie thrombotique.

Renal dysfunction may influence outcomes after pulmonary embolism (PE). We determined the incremental value of adding renal function impairment (estimated glomerular filtration rate, eGFR <60 ml/min/1.73m2) on top of the 2019 ESC prognostic model, for the prediction of 30-day all-cause mortality in acute PE patients from a prospective, multicenter cohort. We identified which of three eGFR formulae predicted death most accurately. Changes in global model fit, discrimination, calibration and net reclassification index (NRI) were evaluated with addition of eGFR. We prospectively included consecutive adult patients with acute PE diagnosed as per ESC guidelines. Among 1,943 patients, (mean age 67.3±17.1, 50.4% women), 107 (5.5% (95% CI 4.5–6.5%)) died during 30-day follow-up. The eGFRMDRD4 formula was the most accurate for prediction of death. The observed mortality rate was higher for intermediate-low risk (OR 1.8, 95% CI 1.1–3.4) and high-risk PE (OR 10.3, 95% CI 3.6–17.3), and 30-day bleeding was significantly higher (OR 2.1, 95% CI 1.3–3.5) in patients with vs without eGFRMDRD4 <60 ml/min/1.73m2. The addition of eGFRMDRD4 information improved model fit, discriminatory capacity, and calibration of the ESC models. NRI was significantly improved (p<0.001), with 18% reclassification of predicted mortality, specifically in intermediate and high-risk PE. External validation using data from the RIETE registry confirmed our findings (Table). Addition of eGFRMDRD4-derived renal dysfunction on top of the ESC prognostic algorithm yields significant reclassification of risk of death in intermediate and high-risk PE. Impact on therapy remains to be determined. Type of funding source: Private grant(s) and/or Sponsorship. Main funding source(s): BMS-Pfizer Alliance, Bayer Healthcare

Backgrounds: Renal impairment is associated with an increased risk for bleeding in patients receiving anticoagulant therapy for venous thromboembolism (VTE), and severe renal impairment preclude the use of oral direct anticoagulants. It is unknown if the formula used to assess renal function individualize the same population of patients with severe renal impairment. Methods: We used the RIETE registry to compare the clinical characteristics and outcomes during the first 3 months of anticoagulation in VTE patients with severe renal impairment according to the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) or the Cockcroft and Gault (CG) formulas. Severe renal impairment was considered in patients with glomerular filtration rate (GFR) estimated <30 mL/min according to CG formula, or <30 mL/min/1,73m² according to CKD-EPI formula. The primary outcome was major bleeding. Findings: As of October 2017, among 41,796 patients recruited in RIETE, 2,772 (6·6%) had GFR estimated < 30 ml/min according to both formulas, 1,227 (2·9%) according to CG formula only and 677 (1·6%) according to CKD-EPI formula only. The remaining 36,719 patients (88%) had GFR >30 ml/min according to both formulas. During the first 3 months of anticoagulation, the rates of major bleeding were 10·7%, 8·0%, 9·0% and 4·2%, respectively (p<0·001 for all). The mortality rates were 23·7%, 20·0%, 12·6% and 7·0%, respectively.Interpretation: Combining the two formula to assess renal function may help to individualized more patients at risk of major bleeding under anticoagulant therapy.Funding Statement: Sanofi Spain supported this Registry with an unrestricted educational grant, and Bayer Pharma AG’s support was limited to the part of RIETE outside Spain, which accounts for a 25·31% of the total patients included in the RIETE Registry.Declaration of Interests: Dr. Catella-Chatron reports non-financial support from BRISTOL-MYERS SQUIBB, from null, outside the submitted work. Dr. Bertoletti reports personal fees and non-financial support from BAYER, personal fees and non-financial support from LEO-PHARMA, personal fees and non-financial support from ASPEN, personal fees and non-financial support from BMSPFIZER, non-financial support from DAIICHI, outside the submitted work. Dr. Mismetti reports grants, personal fees and other from BAYER, personal fees from DAIICHI SANKYO, personal fees from BMS/PFIZER, personal fees from BOEHRINGER INGELHEIM, personal fees from SANOFI, outside the submitted work. Dr. Ollier, Dr. Samperiz, Dr. Soler, Dr. Suriñach, Dr. Mahe, Dr. Lorente, Dr. Braester and Dr. Monreal have nothing to disclose. Ethics Approval Statement: All patients provided oral or written consent according to the requirements of the Ethics Committee at each hospital.