The long-term management of patients after pulmonary embolism (PE) remains a major challenge, owing to the risk of persistent symptoms, complications, and recurrence. Residual pulmonary vascular obstruction (RPVO) is common, affecting up to 50% of patients after six months of anticoagulation. Ventilation-perfusion (V/Q) scintigraphy is the imaging modality of choice for detecting RPVO, which typically presents as mismatched perfusion defects, as it offers a sensitivity superior to that of computed tomography pulmonary angiography (CTPA), together with lower radiation exposure and the absence of iodinated contrast agents. V/Q scintigraphy plays a pivotal role in the screening of chronic thromboembolic pulmonary hypertension (CTEPH) and chronic thromboembolic pulmonary disease (CTEPD). Furthermore, follow-up V/Q scintigraphy may aid in the diagnosis of recurrent PE and in predicting recurrence risk.

BACKGROUND:Pulmonary hypertension (PH) frequently complicates interstitial lung diseases (ILDs), adversely affecting outcome. Identifying prognostic factors of patients with PH associated with ILD (ILD-PH) could facilitate early identification of patients who may benefit from PH therapy. METHODS:We included patients with ILD-PH from the prospective HYPID cohort and the French National Pulmonary Hypertension Registry (2007-2022). Univariable and multivariable analyses were performed to identify predictors of 1-year mortality. RESULTS:A total of 581 patients (mean age 69.4±9.3 years; 450 males) were analysed. ILD diagnoses were combined pulmonary fibrosis and emphysema (CPFE) syndrome (30.8%), idiopathic pulmonary fibrosis (29.6%), unclassifiable ILD (13.1%) and fibrotic hypersensitivity pneumonitis (10.3%). Mean pulmonary arterial pressure was 40.7±9.1 mmHg and mean pulmonary vascular resistance (PVR) was 7.6±3.5 Wood units (WU). Off-label PH therapy was initiated after initial evaluation in 215 patients (37%). The median transplant-free survival time was 17 (95% CI 15.2-not reached) months. Multivariable analysis identified male sex (p<0.001), World Health Organization functional class (WHO FC) III (p=0.003) or IV (p=0.003), 6-min walk distance (6MWD) ≤228 m (p<0.001), PVR >5 WU (p=0.008) and absence of PH therapy (p<0.001) as independent predictors of death or lung transplantation at 1 year. CONCLUSION:Non-invasive (6MWD and WHO FC) and invasive (PVR) variables are associated with prognosis in patients with ILD-PH, including in patients with CPFE. PH medication might improve outcomes in this patient population.

RATIONALE:Pulmonary arterial hypertension (PAH) leads to heart failure and impaired exercise capacity. Rehabilitation may improve exercise tolerance, but most previous trials were short-term and open-label. OBJECTIVES:To assess the 12-month efficacy and safety of a 3-month supervised rehabilitation program in PAH. MEASUREMENTS AND MAIN RESULTS:Stable patients from nine French PAH centers were enrolled in a prospective cohort without mention of rehabilitation, and thereafter randomized using a Zelen design either to usual follow-up or to a supervised 3-month rehabilitation program, following a second consent for the latter group. The primary endpoint was endurance time at 75% of maximal workload during cardiopulmonary exercise testing at 12 months (NCT02579954).Between 2015 and 2022, 49 patients were enrolled and 47 randomized (mean age 54.7 years; 27 females; 35 idiopathic PAH; mean mPAP 37.1 mmHg; PVR 5.7 UW; CI 3.0 L/min/m2). Twenty-one patients were assigned to rehabilitation. At baseline, 32 were at low risk, with preserved functional capacity (31 had 6-min walk distance >440 m). Mean (SD) endurance time was 8.7 (8.0) min in the rehabilitation group and 8.1 (4.8) min in controls. At 12 months, mean endurance time was 16.8 ± 20.0 minutes in the rehabilitation arm versus 8.0 ± 7.2 minutes in the control arm (adjusted p = 0.047). Clinical worsening risk tended lower with rehabilitation (RR 0.17, 95%CI 0.02-1.27; p = 0.055). No deaths occurred. CONCLUSIONS:In this multicenter trial using a design limiting performance bias, a 3-month supervised rehabilitation program significantly improved exercise endurance at 12 months and may reduce clinical worsening.

Abstract Background Venous thromboembolism (VTE), which encompasses deep vein thrombosis (DVT) and pulmonary embolism (PE), is a frequent disease associated with thrombus formation and vein wall remodeling. Hence, fibrosis might result from endothelial-to-mesenchymal transition (EndMT), characterized by the loss of endothelial markers and the acquisition of mesenchymal markers. In chronic thromboembolic pulmonary hypertension, transforming growth factor (TGFβ), the most potent inducer of EndMT, impairs thrombus resolution. However, the molecular mechanisms implicated in TGFβ signaling in the context of VTE are unknown. We hypothesized that epigenetic processes regulate the TGFβ signaling pathway in endothelial cells promoting EndMT and vascular fibrosis. Aims To determine if the histone deacetylase 6 (HDAC6) regulates the TGFβ signaling pathway in endothelial cells promoting EndMT and delays venous thrombosis. Methods To study the role of HDAC6 in EndMT, endothelial cells were treated with a pharmacological inhibitor (TCS20b) and incubated with TGFβ and thrombin for 2, 3, and 5 days. Real time PCR and Western blot were performed to analyze endothelial and mesenchymal marker expression and TGFβ signaling. An experimental model of VTE was used to study the role of HDAC6 on thrombus size overtime. Animals were treated or not with a specific HDAC6 inhibitor (tubastatin A) for 7 to 21 days. Analysis of RNAseq data sets publicly available were used to confirm our main results. Within group and treatment differences were analyzed using two-way ANOVA and Tukey’s multiple comparisons. Results Expression of the mesenchymal markers, calponin and transgelin, was increased by TGFβ and thrombin. Interestingly these changes were inhibited in presence of TCS20b. TGFβ mediated these effects through ERK1/2 and HDAC6 activation. Inhibition of HDAC6 in vivo reduced thrombus size 7 days after surgery compared to controls. This was associated with reduced expression of the EndMT marker transgelin in endothelial cells compared to the control animals. We found that FN1-EDA expression was associated with EndMT and regulated by HDAC6 in vitro . This marker was also associated with thrombosis in the RNAseq data set that we analyzed and potentially in patients with recurrent DVT. Conclusion We found that HDAC6 regulates EndMT in venous thrombosis and impairs thrombus resolution. HDAC6 also regulates expression FN1-EDA that appears to be a strong marker associated with DVT and DVT recurrence. Thus, HDAC6 might represent an attractive therapeutic target for patients with a high risk of recurrent VTE.

Background:In patients with unprovoked venous thromboembolism (VTE), indefinite anticoagulation is recommended to prevent recurrence but may expose some patients to unnecessary long-term bleeding risk. Current clinical scores and biomarkers have limited discriminative performance, do not capture the time-dependent nature of VTE, and do not incorporate patients' perspectives or support shared decision-making. Objectives:To develop and validate time-dependent, multicomponent risk prediction scores and socio-anthropological scales (TDMI) integrated in a shared decision-making process to optimize long-term anticoagulation management after unprovoked VTE. Methods:MORPHEUS is an international, multidisciplinary research programme conducted in eight European countries. The TDMI will combine clinical, biological, imaging, and pharmacological biomarkers with socio-anthropological scales reflecting patients' lived experiences, preferences, and perceptions of risk. Candidate components will be identified through systematic literature review, Delphi consensus, qualitative interviews with patients and physicians, and pooled analyses of large prospective European VTE cohorts including clinical outcomes, biobanks, and imaging data. Dynamic, multi-level, time-dependent prediction models for recurrent VTE and anticoagulant-related bleeding will be derived using advanced statistical and machine-learning approaches. The clinical effectiveness and acceptability of TDMI integrated in a shared decision-making process will be evaluated in a stepped-wedge cluster randomized trial enrolling 2,400 patients with a first unprovoked VTE. Results:The TDMI is expected to improve individualized risk stratification, reduce unnecessary extended anticoagulation, lower bleeding complications, and improve patient satisfaction, treatment adherence, and quality of life. Conclusion:The MORPHEUS project will support personalized anticoagulation decisions and improve long-term outcomes in patients after unprovoked VTE.

Pulmonary vascular obstruction index (PVOI), assessed using the Qanadli index on computed tomography pulmonary angiography (CTPA) at pulmonary embolism (PE) diagnostic, has been associated with recurrence after unprovoked PE, but its complexity limits routine use. We aimed to evaluate simplified semiquantitative (Sq) measures of initial PVOI for predicting recurrent PE after anticoagulation discontinuation.This post hoc analysis, based on the double-blind, randomized PADIS-PE trial where patients with a first unprovoked PE initially treated during 6 months were allocated to receive either an additional 18-month warfarin or placebo, was restricted on the 180 patients who had PE diagnosed by CTPA. Initial PVOI was assessed using four methods: Qanadli score, modified Qanadli score, anatomical-based SqPVOI1, and lobe-based SqPVOI2. Accuracy and associations with recurrent PE were evaluated using area under the curve (AUC) analysis and Cox regression models.Among the 180 included patients (mean age 66.2 ± 16.5 years; 45.2% female), recurrent PE occurred in 42 patients (36-month median follow-up). Accuracy was comparable across the four PVOI scores, with AUCs ranging from 0.70 to 0.74. All scores showed comparable ability to predict recurrent PE. When using the anatomical-based SqPVOI1, recurrence risk increased progressively with more proximal thrombus location: compared with segmental artery involvement (36-month cumulative incidence, 10.5%; n = 76), risk was 2- to 3-fold with lobar artery involvement (HR 2.90, 95%CI, 1.20-7.05, p = 0.005; 36-month cumulative incidence, 25.6%; n = 63) and 4- to 5-fold increased risk (HR 4.59, 95%CI, 1.85-11.42, p = 0.001; 36-month cumulative incidence, 46.8%; n = 41) with main pulmonary artery involvement.Simplified anatomical assessment of PVOI showed prognostic information comparable to quantitative indices. Further prospective validation is needed.

BACKGROUND:Determining venous thromboembolism (VTE) risk among first-degree relatives (FDRs) of VTE patients requires effective risk assessment. We aimed to evaluate VTE risk in FDRs of index cases (ICs) compared to the general population. METHODS:A cross-sectional family study (France, Canada) and a population-based study in the Brest district (France) were conducted. VTEs were adjudicated by an independent clinical event committee. The standardised incidence ratio (SIR), defined as observed-to-expected ratios of VTE in FDR, and 95% confidence interval (CI) were calculated using an indirect standardisation. Expected numbers of VTE were calculated from age-specific incidence rates in the reference population. RESULTS:Among the 2617 FDRs of 507 ICs with VTE, 123 had VTE (annual incidence: 1.2 per 1000 person-years). Of 367,911 Brest district inhabitants, 576 had VTE (annual incidence: 1.6 per 1000 person-years). Compared with the general population, FDRs had a higher VTE risk when the ICs had unprovoked VTE (SIR 1.31, 95%CI 1.11-1.53), had VTE before 47 years (SIR 3.28, 95%CI 2.69-3.85) or when ≥2 FDRs were affected (SIR 1.51, 95%CI 1.14-1.88). The highest VTE risk in FDRs was observed when ICs had unprovoked VTE and ≥2 affected FDRs (SIR 6.36, 95%CI 5.52-7.20) or when ICs had VTE before 47 and ≥2 affected FDRs (SIR 9.93, 95%CI 7.75-12.12). Factor V Leiden and G20210 prothrombin variant status of ICs had a modest influence. CONCLUSION:FDR VTE risk is significantly higher when the IC had unprovoked VTE, before 47 years, and/or when multiple FDRs were affected, compared to the general population.

BACKGROUND:Venous thromboembolism (VTE) prevention in obstetrics remains a major public health concern. Precise data on the timing of VTE events and which women are at risk are necessary to improve thromboprophylaxis strategies. OBJECTIVES:Primary objective was to determine the incidence of VTE during postpartum. Secondary objectives were: (i) to assess VTE incidence during pregnancy; (ii) to describe VTE risk factors; (iii) to evaluate VTE incidence according to risk stratification and thromboprophylaxis. METHODS:From June 2015 to January 2019, the prospective cohort "HEMOTHEPP" study included all pregnant women aged ≥16 years admitted for delivery after 15 weeks of gestation in the Finistère region of France (6 maternity units) and followed for 3 months postpartum. An ethics committee approved the study. The primary outcome was symptomatic, documented VTEs-deep vein thrombosis (DVT), pulmonary embolism (PE), or unusual site VTE-as adjudicated by an independent committee. RESULTS:Among the 20 238 included women, VTE incidence was 4.9 per 1000 person-years (95% CI, 3.3-7.2) during postpartum and 1.3 per 1000 person-years (95% CI, 0.8-2.0) during pregnancy. Postpartum VTEs included 40.0% isolated PEs, 12.0% PE with DVTs, 12.0% isolated DVTs, and 36.0% unusual site VTEs. Of these events, 32.0% occurred during days 0 to 7, 60.0% during days 8 to 42, and 8.0% during days 43 to 90 postpartum. According to the Royal College of Obstetricians and Gynaecologists risk score, 7978 women (39.5%) were classified as intermediate or high risk of postpartum VTE and eligible for thromboprophylaxis; among them, only 3161 (39.6%) received it. Among intermediate-risk women, VTE incidence was similar with or without thromboprophylaxis: 12.0 and 11.8 per 1000 person-years, respectively. CONCLUSION:Postpartum VTE incidence was twice as high as expected. Thromboprophylaxis during postpartum was underprescribed. The high VTE incidence rate after the first week postpartum and in intermediate-risk women, regardless of thromboprophylaxis, highlights the need for randomized trials to evaluate the benefits of thromboprophylaxis.

Introduction L’hypertension pulmonaire (HTP) peut compliquer les pneumopathies interstitielles diffuses (PID) et en aggraver le pronostic. L’identification de facteurs pronostiques pourrait aider à identifier les patients pouvant bénéficier d’un traitement spécifique de l’HTP-PID. Méthodes Les patients atteints d’HTP-PID enregistrés dans les cohortes HYPID (2002-2017) et dans le registre national français de l’hypertension pulmonaire (2013-2022) ont été inclus. Des analyses univariées et multivariée ont été réalisées pour identifier les facteurs prédictifs de la mortalité à 1 an. Les résultats sont donnés en moyenne±écart-type. Résultats n=581 patients ont été inclus, d’âge moyen 69,4±9,3ans. Les diagnostics de PID les plus fréquents étaient le syndrome emphysème-fibrose (SEF) (n=179, 31 %), la fibrose pulmonaire idiopathique (FPI) (n=172, 30 %), les PID inclassables (n=76, 13 %) et les pneumopathies d’hypersensibilité (n=60, 10 %). La pression artérielle pulmonaire moyenne était de 41±9mmHg, l’index cardiaque (IC) était de 2,5±0,7 L/min/m2, et les résistances vasculaires pulmonaires (RVP) étaient de 7,6±3,5 unités Wood (UW). Un traitement spécifique pour l’hypertension pulmonaire a été débuté après l’évaluation initiale chez 214 patients (37 %), le plus souvent par IPDE5 en monothérapie (n=139, 24 %).En analyse univariée, la survie sans transplantation à 1 an était significativement associée au type de PID (mortalité plus élevée en cas de FPI ou de PINS, p=0,002), au sexe masculin (p=0,023), à une classe fonctionnelle NYHA III ou IV (p<0,001), à une distance de marche des 6minutes (DM6)≤228 m (p<0,001), à une CVF≤70 %pred (p=0,002), à la prescription d’oxygénothérapie au long cours (p=0,002) et à un IC≤2,5L/min/m2 (p=0,039). La prescription d’un traitement spécifique de l’HTP après la première évaluation était significativement associée à une meilleure survie (p<0,001). Des RVP>5 UW n’étaient pas significativement associée à une augmentation de la mortalité.En analyse multivariée, le risque de décès ou de transplantation pulmonaire à 1 an était significativement associé au sexe masculin (Hazard ratio [HR]=2,1, p<0,001), à une classe fonctionnelle NYHA III (HR=1,7) ou IV (HR=2,4, p=0,003), à une DM6≤228 m (HR=1,7, p<0,001), à des RVP>5 WU (HR=1,6, p=0,008) et à l’absence de prescription d’un traitement spécifique de l’HTP après la première évaluation (HR=2,5, p<0,001). Conclusion L’association des RVP et de variables cliniques simples permet de prédire la mortalité dans l’HTP-PID. Les traitements spécifiques de l’HTP pourraient améliorer le pronostic de ces patients.

Introduction Previous studies reported an annual incidence rate of superficial vein thrombosis (SVT) of 0.6/1000 patient-years in obstetrical context. Risk factors of SVT and subsequent risk of venous thromboembolism (VTE) are uncertain. Objective To determine the annual incidence rate of SVT during pregnancy and postpartum, the risk of subsequent VTE and SVT risk factors. Method The “HEMOrrhage and venous THromboEmbolism in PostPartum–HEMOTHEPP” study (NCT02443610) is a French multicenter prospective cohort study of 20,238 unselected pregnant women who delivered at a term >15-week gestation from 1st June 2015 to 31st January 2019 with three-month postpartum follow-up. Study was approved by the Ethics Committee of Brest University Hospital in June 2014. Results Among the 20,238 included women, 56 (annual incidence 2.8/1000 person-years) had isolated and documented SVT: 18 during pregnancy (annual incidence 1.2/1000 person-years) and 38 during postpartum (annual incidence 7.5/1000 person-years). Among the 3722 women who received thromboprophylaxis, 8 had SVT (all in postpartum): none had SVT history, and one had VTE history. Among the 16,516 women without thromboprophylaxis, 48 had SVT (18 during pregnancy and 30 during postpartum): five had SVT history and two had VTE history. One woman with SVT during pregnancy had recurrent SVT during early postpartum despite thromboprophylaxis and none had subsequent VTE. As compared to women with VTE, women with SVT were younger, had healthy weight and had fewer cesarean delivery. Conclusion We found an annual incidence rate of SVT in obstetrical context four-times higher than previously described. The risk of recurrent SVT or VTE during the same pregnancy was low. For women with history of SVT, thromboprophylaxis appeared efficient to prevent recurrent SVT or VTE. SVT risk factors may differ from those for VTE.

Objectifs Le risque de survenue d’une maladie veineuse thromboembolique (MVTE) est augmenté en contexte obstétrical. En raison des nombreux facteurs de risque (FDR) impliqués dans la survenue de cette pathologie et de la nécessité d’une réévaluation fréquente du risque en ante partum et en post-partum, des scores de prédiction du risque de MVTE ont été développés pour faciliter la démarche de prescription d’une thromboprophylaxie. Cet article propose une synthèse critique de ces scores. Méthodes Une revue de la littérature sur PUBMED utilisant les termes ([pregnancy OR postpartum] AND [score OR risk OR model prediction] AND [venous thromboembolism OR pulmonary embolism OR deep vein thrombosis]) – a recensé les articles publiés entre janvier 2000 et mai 2024. Résultats Parmi 2532 articles, quatorze scores ont été retenus. Certains s’appliquent à des sous-populations spécifiques en ante partum et pendant le post-partum : (i) femmes à haut risque de MVTE; (ii) femmes à haut risque de MVTE et de complications vasculo-placentaires ; (iii) femmes atteintes d’obésité ; certains scores ne sont utilisables qu’en post-partum : (i) femmes à haut risque d’un premier épisode ; (ii) femmes ayant accouché par voie basse ou césarienne ; (iii) femmes ayant accouché par césarienne uniquement. D’autres scores s’adressent à une population non sélectionnée. La méthodologie utilisée pour leur construction, le degré de validation, les FDR considérés et les stratégies thérapeutiques proposées selon la classification des femmes enceintes diffèrent également. Conclusion L’utilisation d’un score de prédiction du risque de MVTE est recommandée depuis 2008. Son importance en pratique clinique pour l’évaluation du risque de MVTE et la prescription d’une thromboprophylaxie adéquate est documentée. L’utilisation d’un seul score applicable à toutes les patientes, tant pendant la grossesse que le post-partum, paraît plus adaptée aux praticiens de l’obstétrique. Il sera utilisé par l’ensemble de l’équipe à chacune des consultations et/ou hospitalisations.

Chronic thromboembolic pulmonary hypertension (CTEPH) is a severe complication of pulmonary embolism (PE), often diagnosed late due to nonspecific symptoms and limitations of current screening tools like V/Q scintigraphy. This study investigated whether computational fluid dynamics (CFD)-derived hemodynamic parameters, specifically time-averaged wall shear stress (TAWSS) and oscillatory shear index (OSI), in the proximal pulmonary arteries could serve as noninvasive biomarkers for CTEPH and chronic thromboembolic disease without pulmonary hypertension (CTEPD, non-CTEPH with V/Q mismatches). We retrospectively analyzed 90 patients (30 CTEPH, 30 CTEPD, and 30 controls without mismatch) using patient-specific 3D CFD models reconstructed from CTPA, with RCR boundary conditions tuned to RHC data. We found significantly reduced median TAWSS in CTEPH (16.5 dyn/cm2) and CTEPD (27.5 dyn/cm2) groups compared to controls (42.0 dyn/cm2) (p < 0.001), with TAWSS also significantly lower in CTEPH versus CTEPD. OSI showed no significant inter-group differences. Importantly, TAWSS exhibited a strong inverse correlation with V/Q mismatch status (ρ = -0.673, p < 0.001). ROC analysis revealed that TAWSS accurately predicted perfusion mismatches (AUC = 0.918), with an optimal cutoff of 27.0 dyn/cm2 yielding 100.0% specificity and 70.0% sensitivity. These findings demonstrate that CFD-derived proximal pulmonary artery TAWSS is a promising noninvasive indicator of chronic thromboembolic burden, including subclinical perfusion abnormalities, offering a potential tool to enhance early detection and management of CTEPH.

The pathophysiology of residual pulmonary vascular obstruction (RPVO) and recurrent venous thromboembolism (VTE) after unprovoked pulmonary embolism (PE) remains poorly understood. The purpose was to evaluate fibrinolytic and tissue remodeling markers as indicators of RPVO and recurrence after a first unprovoked PE. Analyses were conducted in the 18 to 70-year-old patients included in the PADIS-PE trial, with a pulmonary vascular obstruction (PVO) index ≥ 30

Background: In patients with pulmonary embolism (PE), identifying predictors of recurrence is important to risk-stratify patients and tailor anticoagulation duration. After PE, a significant proportion of patients demonstrate residual pulmonary vascular obstruction (RPVO) on lung imaging. However, the exact prognostic significance of RPVO for venous thromboembolism recurrence remains unclear. Objectives: The primary objective is to assess whether RPVO on ventilation/perfusion (V/Q) single photon emission computed tomography (SPECT)/CT imaging after completion of 3 to 6 months of anticoagulation is an independent predictor of venous thromboembolism recurrence in patients with PE. Methods: The PRONOSPECT trial is a prospective multicenter cohort study. Participants are patients who experienced an objectively proven PE, provoked by a minor transient risk factor or unprovoked; who have been treated with anticoagulant therapy for 3 to 6 uninterrupted months; and for whom anticoagulation will not be prolonged. A standardized baseline patient assessment will be conducted including V/Q SPECT/CT imaging, collection of other potential predictor variables, and a functional evaluation. Anticoagulants will be withdrawn at the 3- or 6-month points from diagnosis and patients will be followed up for up to 2 years. Conclusion: The PRONOSPECT cohort study has the potential to determine whether the presence of RPVO on V/Q SPECT/CT imaging predicts the risk of recurrence in patients with PE in whom there remains a doubt on duration of anticoagulation.

Background: Apixaban and rivaroxaban are approved for the initial and extended treatment of venous thromboembolism (VTE). Both drugs have shown similar efficacy to prevent recurrent VTE, but cohort studies and a recent randomized controlled trial (RCT) suggest that, over the first 3 months of treatment, rivaroxaban use is associated with a significantly higher risk of clinically relevant bleeding (CRB) than apixaban. Whether the same phenomenon is observed during extended treatment, either at full or reduced dose, is unknown. Methods: The RENOVE open-label multicenter RCT compared full-dose vs reduced-dose direct oral anticoagulants in patients with VTE who had completed at least 6 months of full-dose treatment and had an indication for extended anticoagulation (Lancet 2025, doi: 10.1016/S0140-6736(24)02842-3). Apixaban or rivaroxaban were permitted in the trial, and randomization was stratified according to the drug used. In this post hoc analysis, we aimed to compare the risk of bleeding between patients who received full-dose apixaban (5 mg bid) vs full-dose rivaroxaban (20 mg daily), and in patients who received reduced-dose apixaban (2.5 mg bid) vs reduced-dose rivaroxaban (10 mg daily). The primary endpoint for this analysis was CRB, and the primary outcome measure was the 5-year cumulative incidence of CRB. The incidence of recurrent VTE, major bleeding, the composite of CRB and recurrent VTE, arterial events and death from any cause were secondary outcome measures. Except for the effect of dose reduction, hazard ratios (HR) were adjusted on center, age, sex, BMI, and use of antiplatelet drugs. Results: Of 2,768 patients in the intention-to-treat population, 1,385 patients assigned to full-dose received apixaban (n=630) or rivaroxaban (n=755), and 1383 patients assigned to reduced-dose received apixaban (n=625) or rivaroxaban (n=758). Baseline characteristics were broadly well-balanced between patients given apixaban or rivaroxaban, but median age (66.5 vs 62.6 years), the proportion of women (38.7 vs 32.1%) and proportion of patients with BMI ≥30 kg/m² (32.6 vs 28.8%) were slightly higher in patients given apixaban than in those given rivaroxaban. The maximum follow-up was 5 years, with a median of 37 months. In the full-dose subgroups, the 5-year cumulative incidence of CRB was 16.5% in patients given apixaban vs 14.4% in patients given rivaroxaban (adjusted HR [aHR] 1.02, 95% confidence interval [CI] 0.72-1.43). In the reduced-dose subgroups, the 5-year cumulative incidence of CRB was 11.0% in patients given apixaban vs 9.0% in patients given rivaroxaban (aHR 1.31, 95% CI 0.85-2.01). The 5-year cumulative incidence of major bleeding events was not significantly different between patients on apixaban or rivaroxaban, both in the full-dose subgroups (4.6% vs 3.5%, respectively, aHR 1.35, 95%CI 0.69-2.67) and reduced-dose subgroups (3.0% vs 1.6%, respectively, aHR 0.85, 95%CI 0.28-2.59). The 5-year cumulative incidence of recurrent VTE in the full-dose subgroups was 2.0% with apixaban vs 1.7 % with rivaroxaban (aHR 1.22, 95% CI 0.37-3.99), and 1.4% vs 2.7% in the apixaban and rivaroxaban reduced-dose subgroups, respectively (aHR 0.85, 95%CI 0.32-2.28). There was no significant difference between the two drugs at full or reduced dose in the incidence of the composite of CRB and recurrent VTE, arterial thromboembolic events, and death from any cause. Finally, the effect of dose reduction was consistent across the two drugs regarding the risk of CRB (aHR 0.68 [95%CI 0.47-0.98] for apixaban vs 0.57 [0.40-0.81] for rivaroxaban), the risk of VTE recurrence (aHR 1.33 [0.42-4.19] for apixaban vs 1.34 [0.55-3.27] for rivaroxaban), and the composite of CRB and VTE recurrence (aHR 0.74 [0.52-1.05] for apixaban vs 0.64 [0.46-0.89] for rivaroxaban). Conclusion: In this post hoc analysis of the strata of a large RCT of patients with VTE who had completed at least 6 months of full-dose anticoagulation and had an indication for extended treatment, apixaban and rivaroxaban showed similar safety profiles at 5 years, both in the full- and reduced-dose subgroups comparisons, while dose reduction showed similar benefit on CRB risk with both drugs. In contrast with the first months of full-dose anticoagulation, rivaroxaban proved as safe as apixaban during extended treatment, whether at full or reduced dose. Ideally, these results would need to be confirmed in a specific randomized trial.

Introduction Symptomatic postpartum ovarian vein thrombosis (sPOVT), an unusual site of venous thromboembolism (VTE), is a rare complication occurring in 1/500 deliveries, with uncertain prognosis. Objective To evaluate: (i) the risk factors for sPOVT; (ii) the short-term prognosis, in terms of extension to the inferior vena cava and the left renal and association with pulmonary embolism (PE) or deep vein thrombosis (DVT); and (iii) the risk of recurrent VTE after resuming anticoagulation. Method A review of all documented cases of sPOVT was conducted using data of two French multicenter prospective cohorts of 20,238 unselected pregnant women and 7102 adult patients with VTE (NCT02443610–NCT04297085). All sPOVT diagnoses, VTE recurrences and maternal deaths were reviewed and validated by an independent clinical events committee. The Ethics Committee of Brest University Hospital approved the study protocols. Written informed consent was obtained from all participants before inclusion. Results Among the 13 women with sPOVT, the main VTE risk factors were maternal age ≥35 years (n=6;46.2%), obesity (n=3;23.1%), VTE family history (n=4;30.4%), multiple pregnancy (n=3;23.1%), preterm delivery (n=4;30.4%), caesarean delivery (n=3;23.1%) and postpartum infection (n=9;69.2%). At sPOVT diagnosis, four (30.8%) women presented extension to the inferior vena cava or the left renal vein. Among them, one had concomitant PE and one had thrombosis in the contralateral renal vein. None of them had concomitant DVT. During the median (IQR) follow-up of 6.1 years (3.0–7.3), after resuming anticoagulation, one patient had recurrent VTE despite thromboprophylaxis (i.e. muscular vein thrombosis after surgery five years after sPOVT) and one patient died from Hodgkin's lymphoma without VTE recurrence five years after sPOVT. Conclusion sPOVT appeared frequently associated with proximal clot extension and/or with PE or DVT. These observations support that sPOVT requires early diagnosis and effective anticoagulation for a minimum of three months as recommended for proximal DVT and PE. The risk of recurrence was low, so treating sPOVT similarly to provoked PE or DVT for up to six months seems appropriate. Given the close association between postpartum infection and sPOVT, the thrombotic risk needs to be regularly reassessed during postpartum.

Introduction Après un premier épisode d’embolie pulmonaire non provoquée, déterminer les patients à risque de récidive est important. Un index d’obstruction vasculaire pulmonaire (PVOI)≥40 % est connu pour être un facteur de risque indépendant de récidive d’embolie pulmonaire et est calculé par des radiologues spécialisés en vasculaire, en utilisant le score de Qanadli, sur les angioscanners thoraciques. Le but de notre étude était de calculer et d’évaluer les performances d’un score semi-quantitatif d’obstruction vasculaire sur le risque de récidive d’embolie pulmonaire après l’arrêt du traitement pour un premier épisode d’embolie pulmonaire non provoquée. Méthodes Les analyses ont été réalisées sur l’étude randomisée, en double aveugle, PADIS-PE, dans un sous-groupe de 180 patients, ayant présenté un premier épisode d’embolie pulmonaire non provoquée diagnostiquée par angioscanner thoracique, traités durant six mois puis randomisés pour recevoir soit dix-huit mois supplémentaires de Warfarine soit un placebo. Le PVOI a été calculé selon quatre méthodes : premièrement le score de Qanadli, secondairement le score de Qanadli modifié, troisièmement le SqPVOI1 score anatomique et quatrièmement le SqPVOI2 un score semi-quantitatif. La corrélation a été calculé pour chaque score en prenant le score de Qanadli pour référence, et le risque de récidive d’EP évalué. Résultats Au total, 42 patients ont présenté une récidive d’embolie pulmonaire. Nous avons trouvé une précision et une capacité à prédire la récurrence d’embolie pulmonaire similaire entre le PVOI estimé par la localisation anatomique du thrombus et celui du score de Qanadli. Nous avons également mis en évidence un risque accru de récidive avec la proximalité du thrombus, avec un risque 2 à 3 fois plus élevé avec l’atteinte d’une artère lobaire (HR 2,90, IC95 % 1,20–7,05, p=0,005) et un risque 4 à 5 fois plus élevé (HR 4,59, IC95 % 1,85–11,42, p=0,001) avec une artère pulmonaire comparativement à une artère segmentaire (Tableau 1). Conclusion Nous avons trouvé un risque de récidive d’embolie pulmonaire accru chez les patients dont le thrombus se trouvait dans l’artère pulmonaire ou lobaire, par rapport à une localisation segmentaire. L’approche anatomique du calcul du PVOI est similaire à la mesure quantitative pour prédire la récidive de l’embolie pulmonaire.

Diagnosing pulmonary embolism (PE) in patients with chronic obstructive pulmonary disease (COPD) exacerbation is challenging due to similarities in clinical symptoms. The aim of this study was to evaluate predictors of PE and to derive and validate a COPD-specific PE diagnostic strategy. A post-hoc analysis of the PEP trial, a prospective multicenter study of patients with COPD hospitalized with acutely worsening respiratory symptoms, was conducted. The outcome predicted was PE at admission. Univariable and multivariable analyses were conducted to evaluate predictors of PE. Receiver operating characteristic curves were computed to determine the most discriminant D-dimer cut-offs. The COPD-specific PE diagnostic strategy was externally validated in the independent SLICE trial cohort. A total of 734 patients were included. At admission, the prevalence of PE and/or proximal deep venous thrombosis (DVT) was 6.5% (95%CI 5.0–8.6%). A COPD-specific PE diagnostic strategy consisting of a 3-item score (type of COPD exacerbation, alternative diagnosis less likely than PE, and clinical signs of DVT) combined with D-dimer at specific cut-offs (1,000 μg/L if 0 score item and 500 μg/L if 1 or 2 score items) was derived. The overall diagnostic failure rate was 0.9% (95%CI 0.4–1.9%) and 392 patients (53.4%) would need imaging to rule out PE. The external validation showed comparable results. A COPD-specific PE diagnostic strategy was derived specifically for patients with COPD and acutely worsening respiratory symptoms. Further prospective validation of this diagnostic algorithm is needed prior to integrating it in clinical practice.