Search

Although anticoagulation remains the cornerstone treatment for patients with acute pulmonary embolism (PE), catheter-directed therapy (CDT) has generated great interest as an adjunctive option for those presenting with hemodynamic decompensation or high risk for deterioration and in whom systemic thrombolysis has failed or is contraindicated. However, randomized controlled data supporting the efficacy and safety of CDT in addition to antithrombotic therapy in patients with high-risk and intermediate- to high-risk PE compared with anticoagulation and systemic thrombolysis alone are lacking. This paucity of high-quality data hampers guideline recommendations regarding the optimal therapeutic approach in such patients with PE. The aim of the present paper is to critically appraise the current evidence for CDT in patients with high-risk and intermediate- to high-risk PE and to highlight major areas of innovation in the recent literature. In addition, the authors describe unmet clinical and research needs, potential strategies to resolve these knowledge gaps, and pathways for device selection., Competing Interests: Funding Support and Author Disclosures Dr Piazza has received research grants from Bristol Myers Squibb/Pfizer, Janssen, Alexion, Bayer, Amgen, Boston Scientific, Esperion, and 1R01HL164717-01; and is an adviser to Boston Scientific, Amgen, BCRI, PERC, NAMSA, Bristol Myers Squibb, Janssen, and Regeneron. Dr Sharp is a consultant to Medtronic, Boston Scientific, Philips, Penumbra, and Recor Medical; and has stock options with Althea Medical. 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.)

High-risk pulmonary embolism (PE) refers to a large embolic burden causing right ventricular failure and hemodynamic instability. It accounts for approximately 5% of all cases of PE but contributes significantly to overall PE mortality. Systemic thrombolysis is the first-line revascularization therapy in high-risk PE. Surgical embolectomy or catheter-directed therapy is recommended in patients with an absolute contraindication to systemic thrombolysis. Extracorporeal membrane oxygenation (ECMO) provides respiratory and hemodynamic support for the most critically ill PE patients with refractory cardiogenic shock or cardiac arrest. The complex management of these individuals requires urgent yet coordinated multidisciplinary care. In light of existing evidence regarding the utility of ECMO in the management of high-risk PE patients, a number of possible indications for ECMO utilization have been suggested in the literature. Specifically, in patients with refractory cardiac arrest, resuscitated cardiac arrest, or refractory shock, including in cases of failed thrombolysis, venoarterial ECMO (VA-ECMO) should be considered, either as a bridge to percutaneous or surgical embolectomy or as a bridge to recovery after surgical embolectomy. We review here the current evidence on the use of ECMO as part of the management strategy for the highest-risk presentations of PE and summarize the latest data in this indication., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Introduction: The PE-SARD score (syncope, anemia, renal dysfunction) was developed to predict the risk of major bleeding in the acute phase of pulmonary embolism (PE)., Methods: We analyzed data from 50,686 patients with acute PE included in the RIETE registry to externally validate the PE-SARD score. We calculated the overall reliability of the PE-SARD score, as well as discrimination and calibration for predicting the risk of major bleeding at 30 days. The performance of PE-SARD was compared to the BACS and PE-CH models., Results: During the first 30 days, 640 patients (1.3 %) had a major bleeding event. The incidence of major bleeding within 30 days was 0.6 % in the PE-SARD-defined low-risk group, 1.5 % in the intermediate-risk group, and 2.5 % in the high-risk group, for an OR of 2.22 (95 % CI, 2.02-2.43) for the intermediate-risk group (vs low-risk group), and 3.94 for the high-risk group (vs low-risk group). The corresponding sensitivity was 81.1 % (intermediate/high vs low risk), and specificity was 85.9 % (95 % CI, 85.8-86.1) (low/intermediate vs high risk). The applicability of PE-SARD was consistent across clinically relevant patient subgroups and over shorter time periods of follow-up (i.e., 3 and 7 days). The C-index was 0.654 and calibration was excellent. The PE-SARD bleeding score improved the major bleeding risk prediction compared with the BACS and PE-CH scores., Conclusions: The PE-SARD score identifies PE patients with a higher risk of bleeding, which could assist providers for potentially adjusting PE management, in a framework of shared decision-making with individual patients., Competing Interests: Declaration of competing interest RC, GB, PL, CR, AA and NM have no conflict of interest to declare. GP has received research support from Bristol-Myers Squibb/Pfizer Alliance, Bayer, Janssen, Alexion, Amgen and Boston Scientific Corporation, and consulting fees from Pfizer, Boston Scientific Corporation, Janssen, Prairie Education and Research Cooperative, NAMSA, and Amgen. MM has received research support from Sanofiand Rovi Laboratorios, and consulting fees from Sanofi and Bristol. DJ has served as a speaker for Bristol-Myers Squibb and Sanofi. LB reports grant from Bayer; personal fees and non-financial support from BMS-Pfizer; personal fees and non-financial support from Léo-Pharma; grants, personal fees and non-financial support from MSD; non-financial support from Johnson and Johnson; non-financial support from Opalia-Recordati; personal fees and non-financial support from Viatris; outside the submitted work., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Introduction: We prospectively investigated whether home treatment of pulmonary embolism (PE), is as effective and safe as the recommended early discharge management in terms of outcomes at 3 months., Methods: We performed a post hoc analysis of prospectively and consecutively recorded data in acute PE patients from a tertiary care facility between January 2012 and November 2021. Home treatment was defined as discharge to home directly from the emergency department (ED) after <24 h stay. Early discharge was defined as in-hospital stay of ≥24 h and ≤48 h. Primary efficacy and safety outcomes were a composite of PE-related death or recurrent venous thrombo-embolism, and major bleeding, respectively. Outcomes between groups were compared using penalized multivariable models., Results: In total, 181 patients (30.6 %) were included in the home treatment group and 463 (69.4 %) patients in the early discharge group. Median duration of ED stay was 8.1 h (IQR, 3.6-10.2 h) in the home treatment group, and median length of hospital stay was 36.4 h (IQR, 28.7-40.2) in the early discharge group. The adjusted rate of the primary efficacy outcome was 1.90 % (95 % CI, 0.16-15.2) vs 2.05 % (95 % CI, 0.24-10.1) for home treatment vs early discharge (hazard ratio (HR) 0.86 (95 % CI, 0.27-2.74). The adjusted rates of the primary safety outcome did not differ between groups at 3 months., Conclusions: In a non-randomized cohort of selected acute PE patients, home treatment provided comparable rates of adverse VTE and bleeding events to the recommended early discharge management, and appears to have similar clinical outcomes at 3 months., Competing Interests: Declaration of competing interest IAR, JC, NF, TD, and RC have no relevant conflict of interest to declare. GP receives research grant support from BMS/Pfizer Alliance, Amgen, BSC, Janssen, Bayer, and Alexion. FE declares speaker and consultancy fees from Glaxo Smith Kline and Sanofi, outside of the submitted work. NM declares personal fees from Abbott and St. Jude Medical, grants from Boston-Scientific; grants and personal fees from BMS-Pfizer, personal fees from Bayer-Health-Care, Boehringer-Ingelheim, AstraZeneca, outside the submitted work., (Copyright © 2023. Published by Elsevier Ltd.)

Background: The optimal pulmonary revascularisation strategy in high-risk pulmonary embolism (PE) requiring implantation of extracorporeal membrane oxygenation (ECMO) remains controversial., Methods: We conducted a systematic review and meta-analysis of evidence comparing mechanical embolectomy and other strategies, including systemic thrombolysis, catheter-directed thrombolysis or ECMO as stand-alone therapy, with regard to mortality and bleeding outcomes., Results: We identified 835 studies, 17 of which were included, comprising 327 PE patients. Overall, 32.4% were treated with mechanical pulmonary reperfusion (of whom 85.9% had surgical embolectomy), while 67.6% received other strategies. The mortality rate was 22.6% in the mechanical reperfusion group and 42.8% in the "other strategies" group. The pooled odds ratio for mortality with mechanical reperfusion was 0.439 (95% CI 0.237-0.816) (p=0.009; I 2 =35.2%) versus other reperfusion strategies and 0.368 (95% CI 0.185-0.733) (p=0.004; I 2 =32.9%) for surgical embolectomy versus thrombolysis. The rate of bleeding in patients under ECMO was 22.2% in the mechanical reperfusion group and 19.1% in the "other strategies" group (OR 1.27, 95% CI 0.54-2.96; I 2 =7.7%). The meta-regression model did not identify any relationship between the covariates "more than one pulmonary reperfusion therapy", "ECMO implantation before pulmonary reperfusion therapy", "clinical presentation of PE" or "cancer-associated PE" and the associated outcomes., Conclusions: The results of the present meta-analysis and meta-regression suggest that mechanical reperfusion, notably by surgical embolectomy, may yield favourable results regardless of the timing of ECMO implantation in the reperfusion timeline, independent of thrombolysis administration or cardiac arrest presentation., Competing Interests: Conflict of interest: G. Piazza has received research grant support from Bristol Myers Squibb/Pfizer Alliance, Janssen, Boston Scientific Corporation, Amgen and Bayer, and consulting fees from Amgen, Agile, Pfizer, and the Prairie Education and Research Cooperative. No other author has any conflict of interest to declare., (Copyright ©The authors 2022. For reproduction rights and permissions contact permissions@ersnet.org.)

Multidisciplinary pulmonary embolism (PE) response teams have garnered widespread adoption given the complexities of managing acute PE and provide a platform for assessment of trends in therapy and outcomes. We describe temporal trends in PE management and outcomes following the deployment of such a team. All consecutive patients managed by our multidisciplinary PE response team activated by the Emergency Department were included over a 5-year calendar period. We examined temporal trends in management and rates of a composite primary endpoint (all-cause-death, major bleeding, recurrent venous thromboembolism, and readmission) at 30 days and 6 months. We assessed 425 patients between 2015 and 2019. We observed an increase in PE acuity and use of systemic thrombolysis. The primary endpoint at 30 days decreased from 16.3% in 2015 to 7.1% in 2019 (adjusted rate ratio per period, 0.63; 95%CI, 0.47-0.84), driven by a decrease in the adjusted rate of major bleeding. Among 406 patients with complete follow-up, the adjusted rate ratio per year for the primary outcome at 6 months was 0.37 (95%CI, 0.19-0.71), driven by a decrease in all-cause mortality. We observed evidence of temporal changes in clinical presentation, therapeutic strategies, and outcomes for acute PE, in parallel to, but not necessarily because of, the implementation of a multidisciplinary response team. Over time, major bleeding, mortality and readmission rates decreased, despite an increase in PE risk category., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background Pulmonary embolism (PE) has a long-term risk of adverse events, which can be prevented by extended anticoagulation. We compared clinical characteristics and outcomes between patients treated with 2-year extended anticoagulation and those who were not, in a population who had completed an initial phase of 3 to 6 months of anticoagulant therapy after acute PE. Methods and Results Observational cohort analysis of patients with PE who survived an initial phase of 3 to 6 months anticoagulation. Primary efficacy outcome was all-cause death or recurrent venous thromboembolism. Primary safety outcome was major bleeding. In total, 858 (71.5%) patients were treated with and 341 (28.5%) were treated without extended anticoagulant therapy during the active study period. Age <65 years, intermediate-high or high-risk index PE, normal platelet count, and the absence of concomitant antiplatelet treatment were independently associated with the prescription of extended anticoagulation. The mean duration of the active phase was 2.1±0.3 years. The adjusted rate of the primary efficacy outcome was 2.1% in the extended group and 7.7% in the nonextended group ( P <0.001) for patients treated with extended anticoagulant therapy. Rate of bleeding were similar between the extended anticoagulant group and the nonextended group. Conclusions Extended oral anticoagulation over 2 and a half years after index PE seems to provide a net clinical benefit compared with no anticoagulation in patients with PE selected to receive extended anticoagulation. Randomized clinical trials are warranted to explore the potential benefit of extended anticoagulation in patients with PE, especially those with transient provoking factors but residual risk.

Systemic thrombolysis for acute pulmonary embolism reduces the risk of death and cardiovascular collapse but is associated with an increased rate of bleeding. The desire to minimize the risk of bleeding events has driven the development of catheter-based strategies for pulmonary reperfusion in pulmonary embolism. These catheter-based strategies utilize lower-dose fibrinolytic regimens or purely mechanical thromboaspiration to expedite removal of the embolus. The most comprehensive data on catheter-based techniques come from trials of ultrasound-facilitated catheter fibrinolysis. This technique relieves right ventricular pressure overload with a lower risk of major bleeding and intracranial haemorrhage than historical rates observed with systemic fibrinolysis in intermediate- to high-risk pulmonary embolism. Two aspiration thrombectomy devices recently demonstrated significant reductions in right ventricle/left ventricle ratio and a low major adverse event rate in patients with intermediate-risk pulmonary embolism. However, further research is required to determine the optimal application of ultrasound-facilitated catheter fibrinolysis and other catheter-based therapies in patients with acute pulmonary embolism., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

Background: Improved prediction of the risk of early major bleeding in pulmonary embolism (PE) is needed to optimize acute management., Research Question: Does a simple scoring system predict early major bleeding in acute PE patients, identifying patients with either high or low probability of early major bleeding?, Study Design and Methods: From a multicenter prospective registry including 2,754 patients, we performed post hoc multivariable logistic regression analysis to build a risk score to predict early (up to hospital discharge) major bleeding events. We validated the endpoint model internally, using bootstrapping in the derivation dataset by sampling with replacement for 500 iterations. Performances of this novel score were compared with that of the VTE-BLEED (Venous Thrombo-Embolism Bleed), RIETE (Registro informatizado de la enfermedad tromboembólica en España; Computerized Registry of Patients with Venous Thromboembolism), and BACS (Bleeding, Age, Cancer, and Syncope) models., Results: Multivariable regression identified three predictors for the occurrence of 82 major bleeds (3.0%; 95% CI, 2.39%-3.72%): Syncope (+1.5); Anemia, defined as hemoglobin <12 g/dL (+2.5); and Renal Dysfunction, defined as glomerular filtration rate <60 mL/min (+1 point) (SARD). The PE-SARD bleeding score was calculated by summing all the components. Overall, 52.2% (95% CI, 50.29%-54.11%) of patients were classified as low bleeding-risk (score, 0 point), 35.2% (95% CI, 33.39%-37.04%) intermediate-risk (score, 1-2.5 points), and 12.6% (95% CI, 9.30%-16.56%) high-risk (score >2.5 points). Observed bleeding rates increased with increasing risk group, from 0.97% (95% CI, 0.53%-1.62%) in the low-risk to 8.93% (95% CI, 6.15%-12.44%) in the high-risk group. C-index was 0.74 (95% CI, 0.73-0.76) and Brier score 0.028 in the derivation cohort. Similar values were calculated from internal bootstrapping. Performance of the PE-SARD score was better than that observed with the VTE-BLEED, RIETE, and BACS scores, leading to a high proportion of bleeding-risk reclassification in patients who bled and those who did not., Interpretation: The PE-SARD bleeding risk score is an original, user-friendly score to estimate risk of early major bleeding in patients with acute PE., (Copyright © 2021 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: Renal dysfunction influences outcomes after pulmonary embolism (PE). We aimed to determine the incremental value of adding renal dysfunction, defined by estimated glomerular filtration rate (eGFR), on top of the European Society of Cardiology (ESC) prognostic model, for the prediction of 30-day mortality in acute PE patients, which in turn could lead to the optimization of acute PE management., Methods: We performed a multicenter, non-interventional retrospective post hoc analysis based on a prospectively collected cohort including consecutive confirmed acute PE stratified per ESC guidelines. We first identified which of three eGFR formulae most accurately predicted death. Changes in global model fit, discrimination, calibration and reclassification parameters were evaluated with the addition of eGFR to the prognostic model., Results: Among 1943 patients (mean age 67.3 (17.1), 50.4% women), 107 (5.5%) had died at 30 days. The 4-variable Modification of Diet in Renal Disease (eGFR MDRD4 ) formula predicted death most accurately. In total, 477 patients (24.5%) had eGFR MDRD4  < 60 ml/min. Observed mortality was higher for intermediate-low-risk and high-risk PE in patients with versus without renal dysfunction. The addition of eGFR MDRD4 information improved model fit, discriminatory capacity, and calibration of the ESC model. Reclassification parameters were significantly increased, yielding 18% reclassification of predicted mortality (p < 0.001). Predicted mortality reclassifications across risk categories were as follows: 63.1% from intermediate-low risk to eGFR-defined intermediate-high risk, 15.8% from intermediate-high risk to eGFR-defined intermediate-low risk, and 21.0% from intermediate-high risk to eGFR-defined high risk. External validation in a cohort of 14,234 eligible patients from the RIETE registry confirmed our findings with a significant improvement of Harrell's C index and reclassification parameters., Conclusion: The addition of eGFR MDRD4 -derived renal dysfunction on top of the prognostic algorithm led to risk reclassification within the intermediate- and high-risk PE categories. The impact of risk stratification integrating renal dysfunction on therapeutic management for acute PE requires further studies.

Objectives: The safety and efficacy of direct oral anticoagulants (DOACs) in intermediate-high risk pulmonary embolism (PE) are unknown. The aims of the present study were to describe outcomes of patients receiving early apixaban or rivaroxaban prescription rather than the recommended delayed prescription strategy., Methods: Retrospective post-hoc analysis based on prospectively collected data from a multicenter cohort including all consecutive PE patients stratified as intermediate-high risk. Group definitions were: early group with DOAC prescription <72 h after admission; delayed group with DOAC prescription between 72 h and discharge. The 30-day primary efficacy outcome was a clinical composite of all-cause death and hemodynamic decompensation. The 30-day primary safety outcome was major bleeding., Results: Among 2411 patients admitted with PE, 302 were treated with a DOAC for an intermediate-high risk PE: 34.2% in the early group and 65.9% in the delayed group. The primary outcome occurred in 4.8% (including 1 death and 4 hemodynamic decompensations) in the early DOAC group and in 9.0% in the delayed DOAC group (OR, 0.44, 95% CI 0.15-1.30). The rate of major bleeding did not differ between groups (OR, 0.99; 95% CI 0.45-2.18). The length of stay was numerically shorter in the early group whereas the other outcomes did not differ significantly., Conclusion: The rate of 30-day outcomes was low in patients receiving a DOAC earlier after admission. Patients in the early DOAC group had a numerically shorter length of stay, with similarly low rates of death and bleeding, and similar RV function recovery compared to the delayed strategy., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Coronavirus disease 2019 (COVID-19) may predispose to venous thromboembolism. We determined factors independently associated with computed tomography pulmonary angiography (CTPA)-confirmed pulmonary embolism (PE) in hospitalised severe COVID-19 patients., Methods: Among all (n=349) patients hospitalised for COVID-19 in a university hospital in a French region with a high rate of COVID-19, we analysed patients who underwent CTPA for clinical signs of severe disease (oxygen saturation measured by pulse oximetry ≤93% or breathing rate ≥30 breaths·min -1 ) or rapid clinical worsening. Multivariable analysis was performed using Firth penalised maximum likelihood estimates., Results: 162 (46.4%) patients underwent CTPA (mean±sd age 65.6±13.0 years; 67.3% male (95% CI 59.5-75.5%). PE was diagnosed in 44 (27.2%) patients. Most PEs were segmental and the rate of PE-related right ventricular dysfunction was 15.9%. By multivariable analysis, the only two significant predictors of CTPA-confirmed PE were D-dimer level and the lack of any anticoagulant therapy (OR 4.0 (95% CI 2.4-6.7) per additional quartile and OR 4.5 (95% CI 1.1-7.4), respectively). Receiver operating characteristic curve analysis identified a D-dimer cut-off value of 2590 ng·mL -1 to best predict occurrence of PE (area under the curve 0.88, p<0.001, sensitivity 83.3%, specificity 83.8%). D-dimer level >2590 ng·mL -1 was associated with a 17-fold increase in the adjusted risk of PE., Conclusion: Elevated D-dimers (>2590 ng·mL -1 ) and absence of anticoagulant therapy predict PE in hospitalised COVID-19 patients with clinical signs of severity. These data strengthen the evidence base in favour of systematic anticoagulation, and suggest wider use of D-dimer guided CTPA to screen for PE in acutely ill hospitalised patients with COVID-19., Competing Interests: Conflict of interest: B. Mouhat has nothing to disclose. Conflict of interest: M. Besutti has nothing to disclose. Conflict of interest: K. Bouiller has nothing to disclose. Conflict of interest: F. Grillet has nothing to disclose. Conflict of interest: C. Monnin has nothing to disclose. Conflict of interest: F. Ecarnot has nothing to disclose. Conflict of interest: J. Behr has nothing to disclose. Conflict of interest: G. Capellier has nothing to disclose. Conflict of interest: T. Soumagne has nothing to disclose. Conflict of interest: S. Pili-Floury has nothing to disclose. Conflict of interest: G. Besch has nothing to disclose. Conflict of interest: G. Mourey has nothing to disclose. Conflict of interest: Q. Lepiller has nothing to disclose. Conflict of interest: C. Chirouze has nothing to disclose. Conflict of interest: F. Schiele has nothing to disclose. Conflict of interest: R. Chopard has nothing to disclose. Conflict of interest: N. Meneveau has nothing to disclose., (Copyright ©ERS 2020.)

Background: Evidence-based clinical practice guidelines define initial management of acute pulmonary embolism (PE) according to risk stratification for early death., Aims: The aims of the present study were to investigate patterns of non-compliance with guidelines for the acute PE treatment, and the associated risk of adverse events., Methods: We performed an observational, multicentre, cohort study of acute PE. Inclusion criteria were all patients with pulmonary embolism admitted to the participating centres between January 2011 and April 2017. The measure of 100% compliance was used to allocate patients in the compliant or non-compliant groups. The primary outcome was all-cause death at 6 months. Secondary outcomes included recurrent venous thromboembolism and major bleeding., Results: In total, 1285 patients were included. Treatment was not in compliance with the guidelines in 172 patients (13.4%). Four factors were identified to be related to non-compliance with the guidelines: shock or hypotension (relative risk [RR] 5.23, 95% confidence interval [CI] 2.64-10.30; P<0.001), renal insufficiency (RR 1.80, 95% CI 1.41-2.28; P<0.001), active cancer (RR 1.35, 95% CI 1.24-1.48; P<0.001) and right ventricular dysfunction at admission (RR 1.06, 95% CI 1.01-1.11; P=0.01). The primary endpoint of all-cause death at 6 months occurred in 62 of 172 patients (36.0%) in the non-compliant group and in 131 of 1113 patients (11.8%) in the compliant group (hazard ratio 2.02, 95% CI 1.45-2.81; P<0.001). The rates of recurrent venous thromboembolism (8.7% vs 1.1%; P<0.001) and major bleeding (13.4% vs 4.9%, P=0.04) from admission to 6-month follow-up were higher in the non-compliant group., Conclusion: Non-compliance with guidelines was independently associated with worse outcomes, including death, recurrent venous thromboembolism and bleeding., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Background: Data regarding the use of direct oral anticoagulants (DOACs) for the treatment of acute pulmonary embolism (PE) are sparse. We conducted a prospective multicentre registry study to describe patterns of DOAC prescription for the treatment of acute PE, and the associated risk of 6-month adverse events in daily practice., Methods: We included all PE patients discharged since the availability of DOACs for the dedicated indication of acute PE treatment. Clinical data and 6-month outcomes, including death, recurrent venous thromboembolism (VTE), bleeding, and chronic thromboembolic pulmonary hypertension (CTEPH) were recorded prospectively. Temporal trends in DOAC prescription were tested., Results: Between 09/2012 and 04/2017, 1082 patients were included: 60.6% (n = 656) were treated with DOACs and 39.4% (n = 426) with another anticoagulant. The prescription rate of DOACs increased sharply just after their release on the market to reach a plateau over time, between 56% and 72% of the total prescription per year in PE patients (p for trend = 0.33). Active malignancy and renal function impairment were factors independently associated with non-prescription of DOACs. Overall, prescription of DOACs was appropriate in 95.3% of patients. The rate of use of non-recommended DOAC doses was 4.2% (n = 28). The rate of death, recurrent VTE, bleeding and CTEPH were 2.4%, 1.2%, 7.2%, and 1.9%, respectively in the DOAC group., Conclusion: The choice to prescribe DOACs or not is related to patient characteristics. The overall appropriateness of prescription is high, while the rate of adverse events observed in patients treated with DOAC is low in our registry., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Dose adjustment of direct oral anticoagulants (DOACs) is not required in the setting of acute PE treatment according to the manufacturer's labelling, beyond the contraindication in severe renal insufficiency. We designed a prospective, multicenter cohort study to investigate the impact of prescription of non-recommended DOAC doses on 6-month adverse events. The primary endpoint was a composite of all-cause death, recurrent VTE, major bleeding, and chronic thromboembolic pulmonary hypertension (CTEPH). In total, among 656 patients discharged with DOACs between 09/2012 and 10/2016, 28 (4.3%) were not treated with a recommended DOAC dose. All the non-recommended DOAC dose prescriptions were under-dosed according to the drug labelling. After multivariate adjustment, age > 70 years, a history of coronary artery disease, creatinine clearance < 50 mL/min and concomitant aspirin therapy were independently associated with non-recommended DOAC dose prescription (C-statistic: 0.82; Hosmer Lemeshow test: 0.50). The primary composite endpoint occurred in 7/28 patients (25.0%) in the non-recommended dose group and in 38/628 patients (6.1%) in the recommended dose group, yielding a relative risk of 3.19 in the non-recommended dose group (95% CI 1.16-8.70; p < 0.001). The higher primary endpoint rate observed in the non-recommended dose group was driven by a significantly higher rate of major bleeding (7.1 vs. 1.4%; p = 0.008), with a non-significant trend toward a higher rate of death (7.1 vs. 2.2%; p = 0.23), recurrent VTE (3.6 vs. 1.4%; p = 0.31), and CTEPH (7.1 vs. 1.6%; p = 0.32). In conclusion, empiric dose reduction of DOACs was associated with 6-month adverse events in our real-life registry.

The long-term impact of persistent pulmonary vascular obstruction after pulmonary embolism (PE) remains unknown. Based on ventilation-perfusion lung scan performed at discharge and 3 months after a first PE, we aimed to investigate the prognostic value on 5-year adverse events of (1) residual pulmonary vascular obstruction (RPVO) at discharge (DIS-RPVO), (2) RPVO at 3 months (3M-RPVO), and (3) relative change in RPVO between the 2 scans (RC-RPVO). We performed a prospective, multicenter cohort study from January 2007 to December 2009 including patients who survived at least 3 months after a PE. RC-RPVO was defined as (DIS-RPVO - 3M-RPVO)/DIS-RPVO. The primary end point was a combined end point at 5 years, composed of all-cause death, recurrent venous thromboembolism, chronic thromboembolic pulmonary hypertension, heart failure, and rehospitalization for cardiac causes. Receiver-operating characteristic curves were computed to define thresholds of DIS-RPVO, 3M-RPVO, and RC-RPVO predictive of the primary combined end point at 5 years. Overall, 241 patients were included (high-risk PE: 11.2%, intermediate-risk PE: 51.8%, low-risk PE: 37%). Mean DIS-RPVO was 27.9 ± 15.1%, mean 3M-RPVO was 10.3 ± 10.8%, and mean RC-RPVO was 61.7 ± 33.4%. At 5 years, 112 patients (46.5%) experienced the combined end point. Both 3M-RPVO ≥15% and RC-RPVO ≤37.5% were independently related to the occurrence of the combined end point at 5 years (p = 0.01 and p = 0.02, respectively). DIS-RPVO did not predict long-term adverse events. In conclusion, RC-RPVO ≤37.5% and 3M-RPVO ≥15% were independently related to the occurrence of adverse events 5 years after a first PE., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Aim: Right ventricular (RV) dysfunction is key for risk stratification in pulmonary embolism (PE). The goal of this study was to compare RV strain values between low and intermediate-to-high risk PE patients assessed by two-dimensional (2D) strain imaging., Methods: The inclusion criterion was a diagnosis of PE confirmed by thoracic computed tomography scan with contrast medium, or by scintigraphy perfusion lung scan. Risk stratification of PE was defined as high when there was hemodynamic instability; intermediate when there were signs of RV dysfunction on echocardiography; and/or elevated troponin I and/or brain natriuretic peptide and low when none of these criteria were present. All patients underwent echocardiography at admission. Apical four-chamber images were analyzed off line using both conventional and 2D strain imaging., Results: Sixty-two patients (mean age 66 years) were prospectively recruited: 33 with low risk PE, 29 with intermediate-to-high risk PE. Global 2D RV strain differed significantly between groups (-13.1% vs. -18.7%, P < 0.01), as did free wall (-12.7% vs. -20.2%, P < 0.016) and septal wall (-13.5% vs. -17.2%, P < 0.01). When the RV was divided into segments, we observed a similar reduction in absolute strain value in the mid and apical free wall segments and in the apical septal wall (-20.3 ± -7.6 vs. -11.8 ± 8.9%; P < 0.01 and -19.6 ± 6.9 vs. -7.4 ± 9.1%; P < 0.01, and -17.7 ± 7.0 vs. 9.9 ± 8.0; P < 0.01, respectively). 2D strain and tricuspid annular plane systolic excursion were significantly related (r(2)  = 0.35, P < 0.01)., Conclusions: Peak RV longitudinal 2D strain is reduced in patients with intermediate-to-high risk PE, especially in the apical and mid segments of the free wall. Global and regional RV longitudinal 2D strain is altered in patients with intermediate-to-high risk PE as compared with low risk PE., (© 2012, Wiley Periodicals, Inc.)

Background: We evaluated prognostic value at 6 months of residual pulmonary vascular obstruction (RPVO) measured before discharge in patients with intermediate- or high-risk pulmonary embolism (PE)., Methods and Results: Prospective registry including 416 consecutive patients with intermediate- or high-risk PE who survived the acute phase. Patients with previous cardiopulmonary disease were excluded. Perfusion lung scans were performed within 6-8 days after the onset of treatment. Residual pulmonary vascular obstruction was graded as the proportion of the lung not perfused. Primary objective was a combined endpoint at 6 months, including death, recurrent PE, and appearance of signs of heart failure. At 6 months, 32 patients (7.7%) had at least one adverse event: 12 deaths (2.9%), 12 recurrent PE (2.9%), and 14 (3.4%) heart failure. Independent predictors of combined endpoint were: cancer [odds ratio (OR) 3.07 (1.22-7.85)]; renal insufficiency at admission [OR: 2.53 (1.17-5.8)]; persistent signs of right ventricular dysfunction at 48 h echography [OR: 3.99 (1.36-11.3)]. The severity of RPVO at discharge was significantly associated with an unfavourable outcome [OR: 2.66 (1.58-3.93)]. The incremental prognostic value of RPVO information was confirmed by significantly improved goodness-of-fit. Threshold RPVO for predicting adverse events was estimated at 35% [area under the curve = 0.76 (0.73-0.82)]. Patients with RPVO greater than threshold at discharge had a significantly higher risk of death at 6 months (P = 0.01)., Conclusions: Residual pulmonary vascular obstruction evaluated before hospital discharge in patients with intermediate- to high-risk PE is a powerful prognostic factor for a 6-month outcome. RPVO ≥35% is associated with an increased risk of adverse events at 6 months.

No data are available on the efficacy and safety of a combination of fondaparinux and thrombolysis in the setting of high to intermediate risk pulmonary embolism (PE). Patients submitted to thrombolysis and fondaparinux, presenting with > or =1 of the following criteria were included: (1) cardiogenic shock, (2) syncope, (3) > or =1 proximal thrombo-embolus at CT scan, (4) positive troponin test, (5) echocardiographic findings indicating right ventricular (RV) dysfunction. In-hospital results included death, recurrent PE, persistent RV dysfunction at 48 h echocardiography, bleeding complications. Twenty seven patients were included; 22 received a 2 h infusion of rt-PA and 5 received a 2 h infusion of streptokinase. Ten patients presented with cardiogenic shock (37%), 8 with syncope (30%), all had RV dysfunction. 82% of patients had an uneventful in-hospital course. One patient died during hospital stay from refractory shock. Thrombolysis failed in 2 patients (7%), requiring successful rescue surgical embolectomy. Bleeding events occurred in 2 patients (7%), of whom 1 required blood transfusion. Despite the small sample size, our data suggest that fondaparinux procures adequate tolerability compared to standard current therapy in combination with thrombolysis in high to intermediate risk PE.