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Background: Right ventricular (RV) function plays a critical role in the pathophysiology and acute prognosis of pulmonary embolism (PE). We analyzed the temporal changes of RV function in the cohort of a prospective multicentre study investigating if an early switch to oral anticoagulation in patients with intermediate-risk PE is effective and safe., Methods: Echocardiographic and laboratory examinations were performed at baseline (PE diagnosis), 6 days and 6 months. Echocardiographic parameters were classified into categories representing RV size, RV free wall/tricuspid annulus motion, RV pressure overload and right atrial (RA)/central venous pressure., Results: RV dysfunction based on any abnormal echocardiographic parameter was present in 84% of patients at baseline. RV dilatation was the most frequently abnormal finding (40.6%), followed by increased RA/central venous pressure (34.6%), RV pressure overload (32.1%), and reduced RV free wall/tricuspid annulus motion (20.9%). As early as day 6, RV size remained normal or improved in 260 patients (64.7%), RV free wall/tricuspid annulus motion in 301 (74.9%), RV pressure overload in 297 (73.9%), and RA/central venous pressure in 254 (63.2%). At day 180, the frequencies slightly increased. The median NT-proBNP level decreased from 1448 pg/ml at baseline to 256.5 on day 6 and 127 on day 180., Conclusion: In the majority of patients with acute intermediate-risk PE switched early to a direct oral anticoagulant, echocardiographic parameters of RV function normalised within 6 days and remained normal throughout the first 6 months. Almost one in four patients, however, continued to have evidence of RV dysfunction over the long term., (© 2022. The Author(s).)

Background: Coronavirus disease 2019 (COVID-19) has shown high morbidity and mortality and the relationship between pulmonary embolism (PE) and COVID-19 is well established in the literature., Methods: We describe the characteristics of a cohort of COVID-19 patients (EP-COV) hospitalized at our Centre with PE, investigating how COVID-19 may have influenced their outcomes, as compared to patients without COVID-19 hospitalized for PE in the same months of 2020 (EP-2020) and 2019 (EP-2019)., Results: EP-COV patients (n=25) were younger (60.5 ± 8.5 vs 71.4 ± 14.5 vs 70.9 ± 11.8 years, p=0.003), more frequently male (76% vs 48% vs 35%, p=0.016), with a lower history of neoplasia (12% vs 47% vs 40%, p=0.028) and more clinically severe (SOFA score 3.4 ± 1.4 vs 2.2 ± 1.4 vs 1 ± 1.1, p<0.001 and PaO2/FiO2 ratio 223.8 ± 75.5 vs 306.5 ± 49.3 vs 311.8 ± 107.5) than EP-2020 (n=17) and EP-2019 patients (n=20). D-dimer and C-reactive protein were higher in EP-COV (p=0.038 e p<0.001, respectively). The rate of concomitant deep vein thrombosis associated with PE did not differ significantly between the three groups. EP-COV patients developed PE more frequently during in-hospital stay than non-COVID-19 patients (p = 0.016). The mortality rate was higher in EP-COV than in EP-2020 and EP-2019 patients (36% vs 0% vs 5%, p=0.019)., Conclusions: In our study, the risk factors for PE in COVID-19 patients seem to differ from the traditional risk factors for venous thromboembolism; EP-COV patients are clinically more severe and display a higher mortality rate than EP-2020 and EP-2019 patients.

Background: Current guidelines recommend a risk-adjusted treatment strategy for the management of acute pulmonary embolism. This is a particular patient category for whom optimal treatment (anticoagulant treatment, reperfusion strategies, and duration of hospitalisation) is currently unknown. We investigated whether treatment of acute intermediate-risk pulmonary embolism with parenteral anticoagulation for a short period of 72 h, followed by a switch to a direct oral anticoagulant (dabigatran), is effective and safe., Methods: We did a multinational, multicentre, single-arm, phase 4 trial at 42 hospitals in Austria, Belgium, France, Germany, Italy, Netherlands, Romania, Slovenia, and Spain. Adult patients (aged ≥18 years) with symptomatic intermediate-risk pulmonary embolism, with or without deep-vein thrombosis, were enrolled. Patients received parenteral low-molecular-weight or unfractionated heparin for 72 h after diagnosis of pulmonary embolism before switching to oral dabigatran 150 mg twice per day following a standard clinical assessment. The primary outcome was recurrent symptomatic venous thromboembolism or pulmonary embolism-related death within 6 months. The primary and safety outcomes were assessed in the intention-to-treat population. The study was terminated early, as advised by the data safety and monitoring board, following sample size adaptation after the predefined interim analysis on Dec 18, 2018. This trial is registered with the EU Clinical Trials Register (EudraCT 2015-001830-12) and ClinicalTrials.gov (NCT02596555)., Findings: Between Jan 1, 2016, and July 31, 2019, 1418 patients with pulmonary embolism were screened, of whom 402 were enrolled and were included in the intention-to-treat analysis (median age was 69·5 years [IQR 60·0-78·0); 192 [48%] were women and 210 [52%] were men). Median follow-up was 217 days (IQR 210-224) and 370 (92%) patients adhered to the protocol. The primary outcome occurred in seven (2% [upper bound of right-sided 95% CI 3]; p<0·0001 for rejecting the null hypothesis) patients, with all events occurring in those with intermediate-high-risk pulmonary embolism (seven [3%; upper bound of right-sided 95% CI 5] of 283). At 6 months, 11 (3% [95% CI 1-5]) of 402 patients had at least one major bleeding event and 16 (4% [2-6]) had at least one clinically relevant non-major bleeding event; the only fatal haemorrhage occurred in one (<1%) patient before the switch to dabigatran., Interpretation: A strategy of early switch from heparin to dabigatran following standard clinical assessment was effective and safe in patients with intermediate-risk pulmonary embolism. Our results can help to refine guideline recommendations for the initial treatment of acute intermediate-risk pulmonary embolism, optimising the use of resources and avoiding extended hospitalisation., Funding: German Federal Ministry of Education and Research, University Medical Center Mainz, and Boehringer Ingelheim., Competing Interests: Declaration of interests FAK reports research grants from Bayer, Bristol-Myers Squibb, Boehringer Ingelheim, Daiichi Sankyo, Merck Sharpe & Dohme, the Netherlands Organisation for Health Research and Development, Actelion, the Dutch Heart foundation, and the Dutch Thrombosis Association, all outside the submitted work. SB reports congress and travel payments from Daiichi Sankyo and Bayer; honoraria from BTG Pharmaceuticals, Boston Scientific, Bayer HealthCare, and LeoPharma; and institutional grants from Sanofi, all outside the submitted work. WA reports research support from Bayer, and participating in advisory boards for Bayer, Boehringer Ingelheim, Daiichi Sankyo, Portola, Janssen, Aspen, and Sanofi all outside the submitted work. MB reports consulting and speaker fees from Bayer Healthcare, Daiichi Sankyo, and Sanofi Aventis outside the submitted work. FC reports research grant support from Bristol-Myers Squibb-Pfizer Alliance; fees for board memberships or symposia from Bayer, Bristol-Myers Squibb-Pfizer Alliance, and Astra Zeneca; and travel support from Bayer, Bristol-Myers Squibb-Pfizer Alliance, Leo Pharma, and Actelion all outside the submitted work. KD reports unrestricted research support and speaker or consultant fees from Janssen outside the submitted work. DD reports speaker's honoraria from Bayer Vital, Daiichi Sankyo, and Bristol-Myers Squibb-Pfizer Alliance; and consulting fees from Bayer Vital and Daiichi Sankyo all outside the submitted work. KE reports lecture fees from AstraZeneca, Bayer Vital, Berlin Chemie, Boehringer Ingelheim, and Novartis; and consulting fees from Bayer Vital, Boehringer Ingelheim, Novartis, and Novo Nordisk all outside the submitted work. GG reports personal fees or research grants, or both, from Bayer, Boehringer Ingelheim, Leo, Merck Sharpe & Dohme, and Pfizer outside the submitted work. MVH reports grants from the ZonMW Dutch Healthcare Fund; and grants and personal fees to the Leiden University Medical Center from Boehringer Ingelheim, Bristol-Myers Squibb-Pfizer Alliance, Bayer Health Care, Aspen, and Daiichi Sankyo, all outside the submitted work. DJ reports serving as an advisor or consultant for Bayer HealthCare Pharmaceuticals, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Leo Pharma, Pfizer, ROVI, and Sanofi; serving as a speaker or a member of a speakers' bureau for Bayer HealthCare Pharmaceuticals, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Leo Pharma, ROVI, and Sanofi; and receiving grants for clinical research from Daiichi Sankyo, Sanofi, and ROVI all outside the submitted work. MK reports speaker fees from Pfizer, Boehringer Ingelheim, and Bayer outside the submitted work. IML reports receiving consulting fees and research grants from, and being a member of scientific advisory boards for AOPOrphan Pharmaceuticals, Actelion-Janssen, Merck Sharpe & Dohme, United Therapeutics, Medtronic, Neutrolis, and Ferrer, in addition to being an investigator in trials involving these companies. ML reports consultant and speaker fees from Actelion, Bayer, Thermo Fisher Scientific, Daiichi Sankyo, Merck Sharpe & Dohme, and Bristol-Myers Squibb-Pfizer Alliance; and project funding from Thermo Fisher Scientific all outside the submitted work. NM reports consulting fees, speaker fees, and project funding from Bayer and Bristol-Myers Squibb-Pfizer Alliance; speaker fees from AstraZeneca and Boehringer Ingelheim; and consulting fees from Abbott and Terumo all outside the submitted work. AOP reports speaker fees from SC Pfizer Romania, Servier Pharma, Novartis Pharma Services Romania, Bayer, and SC Sanience outside the submitted work. AS reports consulting fees from Pfizer outside the submitted work. SS reports consulting fees and speaker fees from Aspen and Boehringer Ingelheim; speaker fees from Bayer and Daiichi Sankyo; and project funding and speaker fees from Bristol-Myers Squibb-Pfizer Alliance all outside the submitted work. K-HS reports speaker and consulting fees from Merck Sharpe & Dohme, Janssen-Cilag, and Abbott outside the submitted work. FV reports research grants from Daiichi Sanyo, Boehringer-Ingelheim, Radiometer, and Biomerieux, outside the submitted work. SVK reports institutional research grants and personal consultancy or speaker fees from Actelion/Janssen, Bayer, Daiichi Sankyo, and Boston Scientific; institutional research grants from Boehringer Ingelheim and Servier; and personal consultancy or speaker fees from Bristol-Myers Squibb-Pfizer Alliance and Novartis all outside the submitted work. All other authors declare no competing interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Despite the availability of updated guidelines for the diagnosis and treatment of venous thromboembolism (VTE), the management of this disorder in clinical practice is often not standardized, given the different degree of compliance with official recommendations by the various involved specialists. The aim of this consensus paper, as a result of a board of experts in thromboembolism, is to define strategies to improve the quality of patients' care and the efficiency of healthcare resources utilization, by means of: (a) analysis of the guidelines for diagnosis and treatment of VTE; (b) analysis of diagnostic and therapeutic algorithms currently used in clinical practice by different specialists; (c) agreement on a common algorithm for diagnosis and treatment of VTE in different clinical settings; (d) definition of the possible role of the new oral anticoagulant agents (NOAC), such as rivaroxaban, based on their potential benefits for both acute and chronic therapy. The so-called "single drug approach" (as opposed to the traditional heparin/VKA combination), which can be adopted with these drugs, makes anticoagulation more convenient for both patients and healthcare providers, without the need for a close monitoring of the hemocoagulative status, and with a concomitant reduction of length of hospitalization and treatment costs. Among NOACs, in this paper we focused on rivaroxaban only because it was the unique available NOAC in Italy for the treatment of VTE at the time the manuscript was written. Concerning rivaroxaban, the results of two phase III, randomized and controlled trials confirm the non-inferiority of this drug compared to standard therapy (enoxaparin/warfarin) for the treatment of patients with pulmonary embolism (EINSTEIN PE Study) or deep vein thrombosis (EINSTEIN DVT Study) in terms of both efficacy and safety, supporting its use as an effective therapeutic option for these disorders.

Aims: The aim of the study is to describe the course of the echocardiographically measured pulmonary artery systolic pressure (PAsP) in a series of patients included in the Italian Pulmonary Embolism Registry (IPER)., Methods: Patients with confirmed PE received an echo-Doppler evaluation within 24 hours from hospital admission and after one year. Pulmonary hypertension (PH) was considered "likely" , "possible" or "unlikely" with a right ventricular-right atrial (RV-RA) pressure gradient>45 mm Hg, between 32 and 45 mm Hg and ≤31 mm Hg and no additional echocardiographic variables suggestive of PH, respectively., Results: We studied 286 patients (169 females and 117 males, mean age 67 ± 15; mean follow-up 387 ± 45 days): 240 had a baseline tricuspid regurgitation (TR) and a RV-RA gradient of variable degree. PH was considered likely, unlikely and possible in 97, 93 and 50 patients respectively. At FU echocardiography, 6 patients (2.1%) had a likely PH and all of them were part of the group of 97 patients with a baseline likely PH; 24 patients (8.4%) had a possible PH, and 67% of them had an initial likely PH. No patients with a baseline unlikely PH or without TR developed a follow-up PH (both likely or possible). The probability to show a likely PH at FU echocardiography for patients with a baseline RV-RA gradient>45 mm Hg was 6.2%, while the probability not to have a likely PH for patients with a baseline RV-RA gradient ≤ 45 mm Hg was 100%., Conclusion: In our study population of patients with acute PE, we observed that those presenting with a baseline echocardiographic RV-RA pressure gradient ≤ 45 mm Hg were completely free from a likely PH after 1-year., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: Registries are essential to obtain information on the whole spectrum of patients with pulmonary embolism (PE). The aim of the Italian Pulmonary Embolism Registry (IPER) is to report on demographics, clinical features, management, and outcomes of patients diagnosed with PE in everyday clinical practice., Methods: Patients with confirmed acute PE were enrolled in a web-based registry, in Cardiology, Emergency or Internal Medicine Departments in 47 hospitals in Italy., Results: Overall, 1716 patients were included, mean age 70 ± 15 years, (14% of the patients were <50 and 43% >75 year old); 57% of female gender and 11.7% hemodynamically unstable at presentation/diagnosis. D-dimer was performed in 1358 patients (80%). Computerized tomographic pulmonary angiogram (CT) was used for diagnosis in the majority of the patients (82.1%), followed by perfusion lung scan (8.6%). Thrombolytic agents were used in 185 (10.8%) patients, percutaneous thrombectomy in 14 (0.8%) and surgery in 2 (0.1%). One hundred sixteen patients died while in-hospital (6.7%), 68 (3.9%) due to PE. Death or clinical deterioration occurred in 138 patients (8.0%). All-cause mortality was 31.8% in hemodynamically unstable patients and 3.4% in hemodynamically stable patients; the corresponding PE-related deaths were 23.3% and 1.4% respectively. Age >75 (HR 1.50, 95% CI 1.01-2.25), immobilization > 3 days before diagnosis of PE (HR 2.54, 95% CI 1.72-3.77) and hemodynamic impairment (HR 6.38, 95% CI 4.26-9.57) were independent predictors for in-hospital death., Conclusions: Patients with PE have a considerable risk of death during the hospital stay, PE being the most common cause of early mortality., (Copyright © 2012 Elsevier Ltd. All rights reserved.)