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BACKGROUND: Venous thromboembolism (VTE), encompassing both deep vein thrombosis (DVT) and pulmonary embolism (PE), is a leading cause of morbidity and mortality worldwide. METHODS: GARFIELD-VTE is a prospective, non-interventional observational study of real-world treatment practices. We aimed to capture the 36-month clinical outcomes of 10,679 patients with objectively confirmed VTE enrolled between May 2014 and January 2017 from 415 sites in 28 countries. FINDINGS: A total of 6582 (61.6 %) patients had DVT alone, 4097 (38.4 %) had PE ± DVT. At baseline, 98.1 % of patients received anticoagulation (AC) with or without other modalities of therapy. The proportion of patients on AC therapy decreased over time: 87.6 % at 3 months, 73.0 % at 6 months, 54.2 % at 12 months and 42.0 % at 36 months. At 12-months follow-up, the incidences (95 % confidence interval [CI]) of all-cause mortality, recurrent VTE and major bleeding were 6.5 (7.0-8.1), 5.4 (4.9-5.9) and 2.7 (2.4-3.0) per 100 person-years, respectively. At 36-months, these decreased to 4.4 (4.2-4.7), 3.5 (3.2-2.7) and 1.4 (1.3-1.6) per 100 person-years, respectively. Over 36-months, the rate of all-cause mortality and major bleeds were highest in patients treated with parenteral therapy (PAR) versus oral anti-coagulants (OAC) and no OAC, and the rate of recurrent VTE was highest in patients on no OAC versus those on PAR and OAC. The most frequent cause of death after 36-month follow-up was cancer (n = 565, 48.6 %), followed by cardiac (n = 94, 8.1 %), and VTE (n = 38, 3.2 %). Most recurrent VTE events were DVT alone (n = 564, 63.3 %), with the remainder PE, (n = 236, 27.3 %), or PE in combination with DVT (n = 63, 7.3 %). INTERPRETATION: GARFIELD-VTE provides a global perspective of anticoagulation patterns and highlights the accumulation of events within the first 12 months after diagnosis. These findings may help identify treatment gaps for subsequent interventions to improve patient outcomes in this patient population. ispartof: THROMBOSIS RESEARCH vol:222 pages:31-39 ispartof: location:United States status: published

Clinical guidelines indicate that in patients with cancer-associated thrombosis (CAT), anticoagulant treatment should be continued beyond 6 months as long as the cancer is active. We aimed to analyse the safety of low-molecular-weight heparin (LMWH) beyond 12 months in patients with CAT.We performed a post hoc analysis of consecutive CAT patients from October 2008 to December 2019. The primary outcome was the rate of clinically relevant bleeding (CRB), and we compared two periods (1-12 vs. 12-24 months). Hazard ratio (HR), competing risk analysis and sensitivity analyses were performed.Of the 588 patients included, 30.1% (n = 177) received LMWH beyond 12 months. The rate of CRB in the first 12 months compared to the 12-24 month period was 3.2 per 100 patients/month (95% CI 2.5-4.1) vs. 0.9 per 100 patients/month (95% CI 0.4-1.5), (P 0.0001). The competing risk analysis of CRB comparing both periods showed a lower sub-distribution hazard ratio (SHR) during the period 12-24 months (SHR: 0.5, 95% CI: 0.3-0.8, P 0.001).In patients with cancer-associated thrombosis under anticoagulant treatment with LMWH, the rate of clinically relevant bleeding and major bleeding were lower beyond 12 months.

Background: The clinical characteristics and outcomes of cancer patients with lower-limb isolated superficial vein thrombosis (SVT) have not been consistently evaluated. Methods: We used data in the RIETE registry to compare the clinical characteristics and 90-day outcomes for patients with: (1) active cancer and lower-limb SVT; (2) active cancer and lower-limb deep vein thrombosis (DVT); (3) lower-limb SVT without cancer. The primary outcomes included subsequent symptomatic SVT, DVT or pulmonary embolism (PE). Secondary outcomes were major bleeding and death. Results: From March 2015 to April 2021, there were 110 patients with cancer and SVT, 1695 with cancer and DVT, and 1030 with SVT but no cancer. Most patients in all subgroups (93%, 99% and 96%, respectively) received anticoagulants, while those with SVT received lower daily doses of low-molecular-weight heparin (114 ± 58, 163 ± 44, and 106 ± 50 IU/kg, respectively). During the first 90 days, 101 patients (3.6%) developed subsequent VTE (PE 47, DVT 41, SVT 13), whereas 72 (2.5%) had major bleeding and 282 (9.9%) died. Among the three groups, 90-day events were, respectively: VTE at rates of 7.3%, 4.0% and 2.4%; major bleeding at rates of 2.7%, 3.9% and 0.3%; mortality at rates of 8.2%, 16% and 0.3%. Between D90 and D180, only one SVT recurrence and one death occurred in SVT cancer patients. In multivariable analysis, cancer was associated with subsequent VTE (HR = 2.04; 1.15–3.62), while initial presentation as SVT or DVT were not associated with a different risk. Conclusions: The risk for subsequent VTE (including symptomatic SVT, DVT or PE) was similar in cancer patients with isolated SVT than in those with isolated DVT.

BACKGROUND: Clinical guidelines suggest continuing anticoagulation therapy for >6 months for patients with active cancer and venous thromboembolism (VTE). However, data regarding the safety of its discontinuation are scarce. OBJECTIVES: To valuate the risk factors and the incidence of recurrent VTE 6 months after the discontinuation of anticoagulation therapy in patients with cancer-associated thrombosis (CAT). METHODS: We performed a retrospective study on consecutive patients with CAT recruited between 2008 and 2019. The primary and secondary outcomes were recurrent VTE at 6 and 12 months, respectively. Sensitivity analyses were conducted to investigate the possible heterogeneity of these effects. RESULTS: A total of 311 patients were included, among whom 33.4% had metastases and 30.8% were still receiving oncological treatment after 6 months of anticoagulant therapy. At 6 and 12 months, the incidences of recurrent VTE were 6.1% (95% CI, 3.5–9.4%) and 8.7% (95% CI, 5.8–12.4%), respectively. Recurrent VTE was more frequent in patients with metastases at 6 (sub-distribution hazard ratio [SHR] 3.83; 95% CI, 1.54–9.52) and 12 months (SHR 5; 95% CI, 2.2–11.5). Patients with incidental VTE had fewer recurrent events at 6 (SHR 0.3; 95% CI, 0.1–0.8) and 12 months (SHR 0.3; 95% CI, 0.1–0.6) after discontinuing the anticoagulant therapy. CONCLUSION: The incidence of recurrent VTE at 6 and 12 months following the discontinuation of anticoagulant therapy is higher in patients with CAT. Patients with metastases were at an increased risk of recurrent VTE, whereas patients with incidental VTE were at a lower risk.

Background: The association between heart rate (HR) and pulmonary embolism (PE) outcomes has not been well studied. Furthermore, optimal cutoffs to identify low-risk and intermediate- to high-risk patients are not well known. Research Question: Does an association exist between baseline HR and PE outcome across the continuum of HR values? Study Design and Methods: The current study included 44,331 consecutive nonhypotensive patients with symptomatic PE from the Registro Informatizado de la Enfermedad TromboEmbólica registry between 2001 and 2021. Outcomes included 30-day all-cause and PE-specific mortality. We used hierarchical logistic regression to assess the association between admission HR and outcomes. Results: A positive relationship was found between admission HR and 30-day all-cause and PE-related mortality. Considering an HR of 80 to 99 beats/min as a reference, patients in the higher HR strata showed higher rates of all-cause death (adjusted OR, 1.5 for HR of 100-109 beats/min; adjusted OR, 1.7 for HR of 110-119 beats/min; adjusted OR, 1.9 for HR of 120-139 beats/min; and adjusted OR, 2.4 for HR of ≥ 140 beats/min). Patients in the lower strata of HR showed significantly lower rates of 30-day all-cause mortality compared with the same reference group (adjusted OR, 0.6 for HR of 60-79 beats/min; and adjusted OR, 0.5 for HR of < 60 beats/min). The findings for 30-day PE-related mortality were similar. For identification of low-risk patients, a cutoff value of 80 beats/min (vs 110 beats/min) increased the sensitivity of the simplified Pulmonary Embolism Severity Index (sPESI) from 93.4% to 98.8%. For identification of intermediate- to high-risk patients, a cutoff value of 140 beats/min (vs 110 beats/min) increased the specificity of the Bova score from 93.2% to 98.0%. Interpretation: In nonhypotensive patients with acute symptomatic PE, a high HR portends an increased risk of all-cause and PE-related mortality. Modifying the HR cutoff in the sPESI and the Bova score improves prognostication of patients with PE.

Randomized controlled trials (RCTs) that conduct subgroup analyses have the potential to provide information on treatment decisions in specific groups of patients from heterogeneous populations. Although we understand several factors can modify the incidence of venous thromboembolism (VTE) and the benefit/risk ratio of anticoagulation treatments, further evidence is warranted to show the heterogeneity of treatment effects in different subgroups of patients.The primary purpose was to evaluate the appropriateness and interpretation of subgroup analysis performed on VTE RCTs reporting pharmacological interventions.A systematic review of RCTs published between January 2017 and January 2022 was conducted. Claims of subgroup effects were evaluated with predefined criteria. High-quality claims of subgroup effect were further analyzed and discussed.Overall, 28 RCTs with a generally low bias risk were included. The purposes of the treatments included pharmacologic thromboprophylaxis (17), therapeutic dose anticoagulation (9), and catheter-directed pharmacologic thrombolysis (2). The evaluated subgroup analyses generally presented: a high number of subgroup analyses reported, a lack of prespecification, and a lack of usage of statistical tests for interaction. The authors reported 13 claims of subgroup effect; only two were considered potentially reliable to represent heterogeneity in the direction or magnitude of treatment effect.Subgroup analyses of VTE RCTs reporting pharmacologic interventions are generally methodologically poor. Most claims of subgroup effect did not meet critical criteria and lacked credibility. Clinicians in this field may proceed with scepticism when assessing claims of subgroup effects due to methodological concerns and misleading interpretations.

We explored the variations in use of imaging modalities for confirming pulmonary embolism (PE) according to the trimester of pregnancy. We included all pregnant patients with confirmed acute PE from RIETE, a prospective registry of patients with PE (03/2001–02/2020). Imaging modalities included computed tomography pulmonary angiography (CTPA), ventilation-perfusion (V/Q) scan, or presence of signs of acute PE along with imaging-confirmed proximal deep vein thrombosis (pDVT) without pulmonary vascular imaging. We compared the imaging modalities to postpartum patients with PE, and other non-pregnant women with PE. There were 157 pregnant patients (age: 32.7 ± 0.5), 228 postpartum patients (age: 33.9 ± 0.5), and 23,937 non-pregnant non-postpartum women (age: 69.5 ± 0.1). CTPA was the most common modality for confirming PE, from 55.7% in first trimester to 58.3% in second trimester, and 70.0% in third trimester. From first trimester to third trimester, V/Q scanning was used in 21.3%, 16.7%, and 18.3% of cases, respectively. Confirmed pDVT along with the presence of signs/symptoms of PE was the confirmatory modality for PE in 21.3% of patients in first trimester, 19.4% in second trimester, and 6.7% in third trimester. The proportion of postpartum patients confirmed with CTPA (85.5%) was comparable to that of non-pregnant non-postpartum women (83.2%). From the first trimester of pregnancy to postpartum period, there was a linear increase in the proportion of patients with PE diagnosed with CTPA (p = 0.039). CTPA was the primary modality for confirming PE in all trimesters of pregnancy, although its proportional use was higher in later stages of pregnancy. • Computed tomography pulmonary angiography (CTPA) was the primary modality of diagnosis in all trimesters of pregnancy among patients with confirmed pulmonary embolism, even in the first trimester. • From the first trimester of pregnancy to postpartum period, there was a linear increase in the proportion of patients with pulmonary embolism who were diagnosed based on CTPA. • In the postpartum period, use of CTPA as the modality to confirm pulmonary embolism was comparable to non-pregnant patients.

[Simple Summary] The duration of anticoagulant treatment for venous thromboembolism in cancer patients is not well defined. The decision to suspend or re-introduce anticoagulation is based on an individual assessment between thrombotic and hemorrhagic risk. In this study, three biomarkers have shown the ability to help the clinician in decision making. Although these results should be evaluated in further studies, they open up a possibility of change in the management of cancer associated thrombosis patients., The most appropriate duration of anticoagulant treatment for cancer-associated venous thromboembolism (CAT) remains unclear. We have conducted a prospective multicenter study in CAT patients with more than 6 months of anticoagulant treatment to predict the risk of venous thromboembolism (VTE) recurrence after anticoagulation discontinuation. Blood samples were obtained when patients stopped the anticoagulation, at 21 days and at 90 days. In each sample we assessed different coagulation-related biomarkers: D-dimer (DD), high-sensitivity C-reactive protein (hs-CRP), P-selectin (PS), phospholipids, soluble tissue factor, factor VIII and the thrombin generation test. It was evaluated 325 CAT patients and 166 patients were included in the study, mean age 64 ± 17 years. VTE recurrence until 6 months after stopping anticoagulation treatment was 9.87% [95% confidence interval (CI): 6–15]. The biomarkers sub-distribution hazard ratios were 6.32 for ratio DD basal/DD 21 days > 2 (95% CI: 1.82–21.90), 6.36 for hs-CRP > 4.5 (95% CI: 1.73–23.40) and 5.58 for PS > 40 (95% CI: 1.46–21.30) after 21 days of stopping anticoagulation. This is the first study that has identified the DD ratio, hs-CRP and PS as potential biomarkers of VTE recurrence in cancer patients after the discontinuation of anticoagulation treatment. A risk-adapted strategy may allow the identification of the optimal time to withdraw the anticoagulation in each CAT patient., This research was funded by Instituto de Salud Carlos III, grant number (PI15/01085; PI18/01640, PI20/00075), Sociedad Española de Trombosis y Hemostasia; Fundación Respira, grant number (140/2013), Fundación Neumosur, grant number (5/2013) and the LEO Pharma Research Foundation.

[EN]: [Background]: Recently, some countries have shown stable trends in lung cancer death rates among women not yet described for Spain. We propose to update lung cancer mortality rates in Spain during the period of 1980–2018 by sex and region. [Methods]: We used lung cancer mortality (International Classification of Diseases code 162 for the 9th edition, and codes C33 and C34 for 10th edition) and population data from the Spanish National Statistics Institute for the period 1980–2018. Age-standardised mortality rates (ASMRs), all ages and 30–64 years, by region and sex were assessed through joinpoint regression. [Results]: During the study period lung cancer ASMRs (all ages) in men decreased -0.4% per annum and increased by 3.1% in women. Recently, ASMR (30–64 years) accelerated its decrease (1992–2007; −0.7 and 2007–2018; −3.5%) in men and slowed its increase (1990–2012; 5.7% and 2012–2018; 1.4%) in women. In men, joinpoint analysis detected an initial period in all Autonomous Communities (ACs) in which the rates significantly increased, followed by a second period in which the rates decreased significantly (12 ACs) or remained stable (4 ACs) since the late 1980s or early 1990s. In women, upward trends in ASMRs (all ages) were observed for the whole period in all the ACs. In 13 ACs, an initial period was detected with joinpoint in which the rates remained stable or significantly decreased, followed by a second period in which the rates increased significantly since the late 1980s or early 1990s. [Conclusions]: Our study shows gender differences in lung cancer mortality trends in Spain. These differences may be explained by the increased use of tobacco among women and the decreased use among men., [ES]: [Antecedentes]: Recientemente, algunos países han mostrado tendencias estables en las tasas de mortalidad por cáncer de pulmón entre las mujeres que aún no se han descrito para España. Proponemos actualizar las tasas de mortalidad por cáncer de pulmón en España durante el período 1980-2018 por sexo y región. [Métodos]: Utilizamos la mortalidad por cáncer de pulmón (código 162 de la Clasificación Internacional de Enfermedades según la novena edición, y los códigos C33 y C34 según la décima edición) y los datos poblacionales del Instituto Nacional de Estadística de España para el período 1980-2018. Las tasas específicas de mortalidad por edad (TEME), para todas las edades y entre los 30 y 64 años, por región y sexo, se evaluaron mediante el análisis de regresión por segmentos. [Resultados]: Durante el período de estudio, la TEME (todas las edades) de cáncer de pulmón disminuyó un −0,4% por año en hombres y aumentó un 3,1% en mujeres. Recientemente, la TEME (30-64 años) aceleró su descenso (1992-2007: −0,7% y 2007-2018: −3,5%) en los hombres y desaceleró su aumento (1990-2012: 5,7% y 2012-2018: 1,4%) en las mujeres. En los hombres, el análisis de regresión por segmentos detectó un período inicial en todas las comunidades autónomas (CA) en el que las tasas aumentaron significativamente, seguido de un segundo período en el que las tasas disminuyeron significativamente (12 CA) o se mantuvieron estables (4 CA) desde finales de la década de los ochenta o principios de los noventa. En las mujeres, las tendencias al alza en la TEME (todas las edades) se observaron durante todo el período en todas las CA. En 13 CA, se detectó con el análisis de regresión un período inicial en el que las tasas se mantuvieron estables o disminuyeron significativamente, seguido de un segundo período en el que las tasas aumentaron significativamente desde finales de los años ochenta o principios de los noventa. [Conclusiones]: Nuestro estudio muestra diferencias de género en las tendencias de mortalidad por cáncer de pulmón en España. Estas diferencias pueden explicarse por el aumento del uso de tabaco en las mujeres y la disminución del uso entre los hombres.

Pulmonary hypertension (PH) treatment decisions are driven by the results of randomized controlled trials (RCTs). Subgroup analyses are often performed to assess whether the intervention effect will change due to the patient’s characteristics, thus allowing for individualized decisions. This review aimed to evaluate the appropriateness and interpretation of subgroup analyses performed in PH-specific therapy RCTs published between 2000 and 2020. Claims of subgroup effects were evaluated with prespecified criteria. Overall, 30 RCTs were included. Subgroup analyses presented: a high number of subgroup analyses reported, lack of prespecification, and lack of interaction tests. The trial protocol was not available for most RCTs; significant differences were found in those articles that published the protocol. Authors reported 13 claims of subgroup effect, with 12 claims meeting four or fewer of Sun’s criteria. Even when most RCTs were generally at low risk of bias and were published in high-impact journals, the credibility and general quality of subgroup analyses and subgroup claims were low due to methodological flaws. Clinicians should be skeptical of claims of subgroup effects and interpret subgroup analyses with caution, as due to their poor quality, these analyses may not serve as guidance for personalized care.

Background: The clinical characteristics and outcomes of cancer patients presenting with lower-limb isolated superficial vein thrombosis (SVT) have not been consistently evaluated.Methods: We used data in the RIETE registry to compare the clinical characteristics and 90-day outcomes in patients with: 1) active cancer and lower-limb SVT; 2) active cancer and lower-limb deep vein thrombosis (DVT); 3) lower-limb SVT without cancer. The primary outcome was the composite of symptomatic subsequent SVT, DVT or pulmonary embolism (PE). Secondary outcomes were major bleeding and death.Results: From March 2015 to April 2021, there were 110 patients with cancer and SVT, 1,695 with cancer and DVT, and 1,030 with SVT but no cancer. Most patients in all subgroups (93%, 99% and 96%, respectively) received anticoagulants, those with SVT received lower daily doses of low-molecular-weight heparin (114±58, 163±44, and 106±50 IU/kg, respectively). During the first 90 days, 101 patients (3.6%) developed subsequent VTE (PE 47, DVT 41, SVT 13), 72 (2.5%) bled and 282 (9.9%) died. Subsequent 90-day events were respectively: VTE 7.3%, 4.0% and 2.4%; major bleeding 2.7%, 3.9% and 0.3%; mortality 8.2%, 16% and 0.3%. After D90 only one SVT recurrence and one death occurred in SVT cancer patients. On multivariable analysis, cancer was an independent predictor for subsequent VTE (HR=2.04; 95%CI: 1.15-3.62). Initial presentation as SVT or DVT were not associated with a different risk.Conclusion: The risk for subsequent VTE (including symptomatic SVT, DVT or PE) was similar in cancer patients with isolated SVT than in those with isolated DVT.

IntroductionThere is currently no validated score capable of classifying cancer-associated pulmonary embolism (PE) in its full spectrum of severity. This study has validated the EPIHANY Index, a new tool to predict serious complications in cancer patients with suspected or unsuspected PE.MethodThe PERSEO Study prospectively recruited individuals with PE and cancer from 22 Spanish hospitals. The estimation of the relative frequency θ of complications based on the EPIPHANY Index categories was made using the Bayesian alternative for the binomial test.ResultsNine hundred patients diagnosed with PE between 2017/2020 were recruited. The rate of serious complications at 15 days was 11.8%, 95% highest density interval [HDI], 9.8-14.1%. Of the EPIPHANY low-risk patients, 2.4% (95% HDI, 0.8-4.6%) had serious complications, as did 5.5% (95% HDI, 2.9-8.7%) of the moderate-risk participants and 21.0% (95% HDI, 17.0-24.0%) of those with high-risk episodes. The EPIPHANY Index correlated with overall survival. Both the EPIPHANY Index and the Hestia criteria exhibited greater negative predictive value and a lower negative likelihood ratio than the remaining models. The incidence of bleeding at 6 months was 6.2% (95% HDI, 2.9-9.5%) in low/moderate-risk vs 12.7% (95% HDI, 10.1-15.4%) in high-risk (p-value=0.037) episodes. Of the outpatients, complications at 15 days were recorded in 2.1% (95% HDI, 0.7-4.0%) of the cases with EPIPHANY low/intermediate-risk vs 5.3% (95% HDI, 1.7-11.8%) in high-risk cases.ConclusionWe have validated the EPIPHANY Index in patients with incidental or symptomatic cancer-related PE. This model can contribute to standardize decision-making in a scenario lacking quality evidence.SummaryWe have validated the EPIPHANY Index in patients with acute, incidental, or symptomatic cancer-related PE. This predictive model of complications can contribute to standardize decision-making in a scenario lacking quality evidence.

On March 11, 2020, the World Health Organization declared Coronavirus Disease 2019 (COVID-19) a pandemic. Till now, it affected 452.4 million (Spain, 11.18 million) persons all over the world with a total of 6.04 million of deaths (Spain, 100,992). It is observed that 75% of hospitalized COVID-19 patients have at least one COVID-19 associated comorbidity. It was shown that people with underlying chronic illnesses are more likely to get it and grow seriously ill. Individuals with COVID-19 who have a past medical history of cardiovascular disorder, cancer, obesity, chronic lung disease, diabetes, or neurological disease had the worst prognosis and are more likely to develop acute respiratory distress syndrome or pneumonia. COVID-19 can affect the respiratory system in a variety of ways and across a spectrum of levels of disease severity, depending on a person's immune system, age and comorbidities. Symptoms can range from mild, such as cough, shortness of breath and fever, to critical disease, including respiratory failure, shock and multi-organ system failure. So, COVID-19 infection can cause overall worsening of these previous respiratory diseases, such as asthma, chronic obstructive pulmonary disease (COPD), interstitial lung disease, etc. This review aims to provide information on the impact of the COVID-19 disease on pre-existing lung comorbidities.

[Background]: The relationship between cancer and venous thromboembolic disease (VTD) are complex because the activated coagulation factors are not only involved in thrombosis but also in malignant processes, such as angiogenesis and metastasis., [Objective]: To compare phenotypes of extracellular vesicles (EVs), and levels of D-dimer, soluble P-selectin (sP-selectin) and antigenic tissue factor (TF) between unprovoked VTD patients, who did not develop cancer during one-year follow-up, and those with advanced stage of cancer but not associated with VTD., [Methods]: A prospective study in which we included 138 unprovoked VTD patients and 67 advanced cancer patients, who did not develop thrombosis. Levels of EVs of different cellular origin (platelet, endothelium and leukocyte), EVs positive for tissue factor (TF) and P-selectin glycoprotein ligand 1 were quantified by flow cytometry. D-dimer, soluble P-selectin (sP-selectin) and antigenic TF were determined by ELISA., [Results]: TF-positive EVs, D-dimer, and sP-selectin were markedly elevated in unprovoked VTD patients compared to cancer patients without association with thrombosis., [Conclusions]: Levels of TF-positive EVs, D-dimer and sP-selectin are able to discriminate between unprovoked VTD patients not related to cancer and cancer patients not associated with VTD. These results could lead to the application of EVs as biomarkers of both diseases., This work was supported by research grants from the Plan Nacional de Investigacion Cient ıfica, Desarrollo e Innovacion Tecnologica (Instituto de Salud Carlos III, Fondo de Investigacion Sanitaria [PI11/02308], Red RIC [RD12/0042/ 0029], Junta de Andalucıa [CVI-6654] and by the Fundacion Investigacion Hospital La Fe, Spain.

Persistent thrombotic lesions are common in patients with pulmonary embolism. These lesions occur on a clinical spectrum, ranging from an asymptomatic course with complete functional recovery to chronic thromboembolic pulmonary hypertension. The concept of chronic thromboembolic disease has emerged in recent years to describe a subgroup of patients with persistent thrombotic lesions who have symptoms on exertion and pulmonary vascular dysfunction, but no pulmonary hypertension at rest. The prevalence of this entity is unknown and the criteria for diagnosing it are not defined. The aim of this article is to analyze post-pulmonary embolism sequelae and review existing evidence on chronic thromboembolic disease, with special emphasis on its diagnosis and therapeutic approach.

The International Initiative on Thrombosis and Cancer is an independent academic working group of experts aimed at establishing global consensus for the treatment and prophylaxis of cancer-associated thrombosis. The 2013, 2016, and 2019 International Initiative on Thrombosis and Cancer clinical practice guidelines have been made available through a free, web-based mobile phone application. The 2022 clinical practice guidelines, which are based on a literature review up to Jan 1, 2022, include guidance for patients with cancer and with COVID-19. Key recommendations (grade 1A or 1B) include: (1) low-molecular-weight heparins (LMWHs) for the initial (first 10 days) treatment and maintenance treatment of cancer-associated thrombosis; (2) direct oral anticoagulants for the initial treatment and maintenance treatment of cancer-associated thrombosis in patients who are not at high risk of gastrointestinal or genitourinary bleeding, in the absence of strong drug-drug interactions or of gastrointestinal absorption impairment; (3) LMWHs or direct oral anticoagulants for a minimum of 6 months to treat cancer-associated thrombosis; (4) extended prophylaxis (4 weeks) with LMWHs to prevent postoperative venous thromboembolism after major abdominopelvic surgery in patients not at high risk of bleeding; and (5) primary prophylaxis of venous thromboembolism with LMWHs or direct oral anticoagulants (rivaroxaban or apixaban) in ambulatory patients with locally advanced or metastatic pancreatic cancer who are treated with anticancer therapy and have a low risk of bleeding.

[Background] The length of hospital stay (LOS) for acute pulmonary embolism (PE) varies considerably. Whether the upfront use of a PE prognostic assessment and management pathway is effective in reducing the LOS remains unknown., [Methods] We conducted a randomised controlled trial of adults hospitalised for acute PE: patients were assigned either to a prognostic assessment and management pathway involving risk stratification followed by predefined criteria for mobilisation and discharge (intervention group) or to usual care (control group). The primary end-point was LOS. The secondary end-points were the cost of prognostic tests and of hospitalisation, and 30-day clinical outcomes., [Results] Of 500 patients who underwent randomisation, 498 were included in the modified intention-to-treat analysis. The median LOS was 4.0 days (interquartile range (IQR) 3.7–4.2 days) in the intervention group and 6.1 days (IQR 5.7–6.5 days) in the control group (p, [Conclusions] The use of a prognostic assessment and management pathway was effective in reducing the LOS for acute PE.

To assess severity markers and outcomes of patients with systemic sclerosis (SSc) with or without pulmonary arterial hypertension (PAH-SSc/non-PAH-SSc), and the impact of interstitial lung disease (ILD) on PAH-SSc. Non-PAH-SSc patients from the Spanish SSc registry and PAH-SSc patients from the Spanish PAH registry were included. A total of 364 PAH-SSc and 1589 non-PAH-SSc patients were included. PAH-SSc patients had worse NYHA-functional class (NYHA-FC), worse forced vital capacity (FVC) (81.2 ± 20.6% vs 93.6 ± 20.6%, P

Among patients hospitalized for an exacerbation of chronic obstructive pulmonary disease (COPD), the SLICE trial showed that the addition of an active diagnostic strategy for pulmonary embolism (PE) to usual care compared with usual care alone did not improve a composite set of health outcomes. The objective of this subanalysis was to determine the frequency and prognostic significance of findings on computed tomography pulmonary angiogram (CTPA) supporting an alternative diagnosis to PE.We analyzed all patients randomized to the intervention in the SLICE trial who received a CTPA that did not show PE. We used multivariable logistic regression to assess the independent association between findings supporting an alternative diagnosis to PE and a composite of readmission for COPD or death within 90 days after randomization.Among the 746 patients who were randomized, this subanalysis included 175 patients in the intervention group who received a CTPA that did not show PE. Eighty-four (48.0%) patients had acute bronchial infection, 13 (7.4%) had lung cancer, 10 (5.7%) had congestive heart failure, 8 (4.6%), 18 (10.3%) had other diagnoses, and 42 (24.0%) had a normal CTPA. In multivariable analysis, findings supporting an alternative diagnosis to PE were not significantly associated with the primary outcome (odds ratio: 0.64; 95% confidence interval: 0.30-1.38; P=0.26).Among patients hospitalized for an exacerbation of COPD, CTPA identified an alternative diagnosis in 76% of the patients. However, specific management of these patients was not associated with improved outcomes within 90 days after randomization.

[Background] Chronic obstructive pulmonary disease (COPD) is a condition resulting from a persistent inflammatory state in the airways even after smoking cessation. Intriguingly, the reasons behind this persistence of the inflammatory influx without smoking exposure have not been fully unraveled. We aimed to explore the hypothesis that systemic inflammation in COPD patients influences lung cell inflammatory response., [Methods] We cultured human lung fibroblast and human airway epithelial cell lines with plasma from COPD patients (four emphysematous-COPD, four asthma-COPD overlap, four chronic bronchitis-COPD, and four bronchiectasis-COPD), and four smokers or ex-smokers without COPD as controls. We measured Interleukine-8 (IL-8), C-reactive protein (CRP) and matrix metalloproteinase-9 (MMP-9) in plasma and culture supernatants by ELISA., [Results] Cells stimulated with plasma from COPD patients and control subjects produced higher CRP, IL-8 and MMP-9 levels, an increase for COPD in CRP(p=0.039) in epithelial cells and IL-8(p=0.039) in fibroblasts and decrease for MMP-9(p=0.039) in fibroblasts. The response was higher in epithelial cells for IL-8(p=0.003) and in fibroblasts for MMP-9(p=0.063). The plasma from chronic bronchitis and bronchiectasis phenotypes induced higher IL-8 in fibroblasts., [Conclusions] Plasma from COPD patients increases the inflammatory response in lung epithelial cells and lung fibroblasts, with a different response depending on the cell type and clinical phenotype., This project has been funded by the Instituto de Salud Carlos III, through the Fondo de Investigacion Sanitaria, Ministry of the Economy, Government of Spain (project number PI12/01576)

SLICE Trial Group., [Importance] Active search for pulmonary embolism (PE) may improve outcomes in patients hospitalized for exacerbations of chronic obstructive pulmonary disease (COPD)., [Objective] To compare usual care plus an active strategy for diagnosing PE with usual care alone in patients hospitalized for COPD exacerbation., [Design, Setting, and Participants] Randomized 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)., [Interventions] Usual 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 Measures] The 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., [Results] Among 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 Relevance] Among 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 Registration] ClinicalTrials.gov Identifier: NCT02238639.

Anemia is a common condition in cancer patients and is associated with a wide variety of symptoms that impair quality of life (QoL). However, exactly how anemia affects QoL in cancer patients is unclear because of the inconsistencies in its definition in previous reports. We aimed to examine the clinical impact of anemia on the QoL of cancer patients using specific questionnaires. We performed a post-hoc analysis of a multicenter, prospective, case-control study. We included patients with cancer with (cases) or without (controls) anemia. Participants completed the European Organization for Research and Treatment of Cancer Quality of Life questionnaire version 3.0 (EORTC QLQ-C30) and Euro QoL 5-dimension 3-level (EQ−5D−3L) questionnaire. Statistically significant and clinically relevant differences in the global health status were examined. From 2015 to 2018, 365 patients were included (90 cases and 275 controls). We found minimally important differences in global health status according to the EORTC QLQ-C30 questionnaire (case vs. controls: 45.6 vs. 58%, respectively, mean difference: −12.4, p &lt, 0.001). Regarding symptoms, cancer patients with anemia had more pronounced symptoms in six out of nine scales in comparison with those without anemia. In conclusion, cancer patients with anemia had a worse QoL both clinically and statistically.

[Background] Previous studies have shown that the arterial wall is a potential source of inflammatory markers in COPD. Here, we sought to compare the expression of acute phase reactants (APRs) in COPD patients and controls both at the local (pulmonary arteries and lung parenchyma) and systemic (peripheral blood leukocytes and plasma) compartments., [Methods] Consecutive patients undergoing elective surgery for suspected primary lung cancer were eligible for the study. Patients were categorized either as COPD or control group based on the spirometry results. Pulmonary arteries and lung parenchyma sections, peripheral blood leukocytes, and plasma samples were obtained from all participants. Gene expression levels of C-reactive protein (CRP) and serum amyloid A (SAA1, SAA2, and SAA4) were evaluated in tissue samples and peripheral blood leukocytes by reverse transciption-PCR. Plasma CRP and SAA protein levels were measured by enzyme-linked immunosorbent assays. Proteins were evaluated in paraffin-embedded lung tissues by immunohistochemistry., [Results]A total of 40 patients with COPD and 62 controls were enrolled. We did not find significant differences in the gene expression between COPD and control group. Both CRP and SAA were overexpressed in the lung parenchyma compared with pulmonary arteries and peripheral blood leukocytes. The expression of SAA was significantly higher in the lung parenchyma than in the pulmonary artery (2-fold higher for SAA1 and SAA4, P=0.015 and P, [Conclusions] The expression of SAA in lung parenchyma is higher than in pulmonary artery and peripheral blood leukocytes. Notably, no associations were noted between lung expression of APRs and their circulating plasma levels, making the leakage of inflammatory proteins from the lung to the bloodstream unlikely. Based on these results, other potential sources of systemic inflammation in COPD (eg, the liver) need further scrutiny., The authors thank the HUVR-IBiS Biobank (Andalusian Public Health System Biobank and ISCIII-Red de Biobanco PT13/0010/0056) for the assessment and technical support provided. This study was financially supported by grants from Fundación de Neumología y Cirugía Torácica del Sur (Neumosur) No. 4/2012 and from the Instituto de Salud Carlos III, Ministerio de Economía (PI12/01576).

We explored the variations in use of imaging modalities for confirming pulmonary embolism (PE) according to the trimester of pregnancy.We included all pregnant patients with confirmed acute PE from RIETE, a prospective registry of patients with PE (03/2001-02/2020). Imaging modalities included computed tomography pulmonary angiography (CTPA), ventilation-perfusion (V/Q) scan, or presence of signs of acute PE along with imaging-confirmed proximal deep vein thrombosis (pDVT) without pulmonary vascular imaging. We compared the imaging modalities to postpartum patients with PE, and other non-pregnant women with PE.There were 157 pregnant patients (age: 32.7 ± 0.5), 228 postpartum patients (age: 33.9 ± 0.5), and 23,937 non-pregnant non-postpartum women (age: 69.5 ± 0.1). CTPA was the most common modality for confirming PE, from 55.7% in first trimester to 58.3% in second trimester, and 70.0% in third trimester. From first trimester to third trimester, V/Q scanning was used in 21.3%, 16.7%, and 18.3% of cases, respectively. Confirmed pDVT along with the presence of signs/symptoms of PE was the confirmatory modality for PE in 21.3% of patients in first trimester, 19.4% in second trimester, and 6.7% in third trimester. The proportion of postpartum patients confirmed with CTPA (85.5%) was comparable to that of non-pregnant non-postpartum women (83.2%). From the first trimester of pregnancy to postpartum period, there was a linear increase in the proportion of patients with PE diagnosed with CTPA (p = 0.039).CTPA was the primary modality for confirming PE in all trimesters of pregnancy, although its proportional use was higher in later stages of pregnancy.• Computed tomography pulmonary angiography (CTPA) was the primary modality of diagnosis in all trimesters of pregnancy among patients with confirmed pulmonary embolism, even in the first trimester. • From the first trimester of pregnancy to postpartum period, there was a linear increase in the proportion of patients with pulmonary embolism who were diagnosed based on CTPA. • In the postpartum period, use of CTPA as the modality to confirm pulmonary embolism was comparable to non-pregnant patients.

Over recent decades, a number of studies have revealed the possible role of different types of diets, as well as the nutritional elements they are made up of, in the pathogenesis of chronic obstructive pulmonary disease (COPD). To date, dietary factors have been identified to play a role in the prevention of COPD, with evidence from antioxidant nutrients, vitamins, and fiber intake. Additionally, certain dietary patterns such as the Mediterranean diet, together with other Western diets, provide evidence of the influence on COPD development, promoting lung health through nutritional approaches, and giving us an opportunity for intervention. The effect of diet on COPD is conveyed by 3 mechanisms: regulation of inflammation, oxidative stress, and carbon dioxide produced/oxygen intake. Current advances have begun to highlight the possible role of diet in modifying gene expression in certain individuals that predisposes them to COPD through epigenetic modifications. The relation between dietary intake and epigenetic factors has therefore outlined nutriepigenomics as a possible missing link in the relation between environmental exposure to smoke and the appearance of a subsequent chronic bronchial obstruction. This review summarizes the evidence regarding the influence of dietary patterns and nutrients and epigenetic regulatory mechanisms on COPD development and prevention with the aim of encouraging clinical research on the impact of dietary modifications on COPD-related clinical outcomes. This review highlights the importance of proposing and carrying out future studies focused on the modulating effects of certain nutrients on epigenetic changes in patients with specific COPD phenotypes (bronchiectasis, emphysema, asthma/COPD, chronic bronchitis), and their individual responses to cigarette smoking, environmental pollution, or other noxious particles. The objectives of these future studies must be directed to the development of novel therapeutic approaches and personalized management of COPD.

Objective: The soluble guanylate cyclase stimulator riociguat is approved for the treatment of adult patients with pulmonary arterial hypertension (PAH) and inoperable or persistent/recurrent chronic thromboembolic pulmonary hypertension (CTEPH) following Phase 3 randomized trials. The EXPosurE Registry RiociguaT in patients with pulmonary hypertension (EXPERT) study was designed to monitor the long-term safety of riociguat in clinical practice. Methods: EXPERT was an international, multicenter, prospective, uncontrolled, non-interventional cohort study of patients treated with riociguat. Patients were followed for at least 1 year and up to 4 years from enrollment or until 30 days after stopping riociguat treatment. Primary safety outcomes were adverse events (AEs) and serious adverse events (SAEs) coded using Medical Dictionary for Regulatory Activities preferred terms and System Organ Classes version 21.0, collected during routine clinic visits and collated via case report forms. Results: In total, 956 patients with CTEPH were included in the analysis. The most common AEs in these patients were peripheral edema/edema (11.7%), dizziness (7.5%), right ventricular (RV)/cardiac failure (7.7%), and pneumonia (5.0%). The most common SAEs were RV/cardiac failure (7.4%), pneumonia (4.1%), dyspnea (3.6%), and syncope (2.5%). Exposure-adjusted rates of hemoptysis/pulmonary hemorrhage and hypotension were low and comparable to those in the long-term extension study of riociguat (Chronic Thromboembolic Pulmonary Hypertension Soluble Guanylate Cyclase–Stimulator Trial [CHEST-2]). Conclusion: Data from EXPERT show that in patients with CTEPH, the safety of riociguat in routine practice was consistent with the known safety profile of the drug, and no new safety concerns were identified. © 2020 The Authors Eli Lilly and Company; Pfizer; Bayer; GlaxoSmithKline; Merck; Actelion Pharmaceuticals; Meso Scale Diagnostics; United Therapeutics Corporation; Novartis Pharma; Merck Sharp and Dohme; GlaxoSmithKline Australia; Deutsche Forschungsgemeinschaft; Grupo Ferrer Internacional, S.A The EXPERT registry was funded by Bayer AG (Berlin, Germany) and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co. Inc., Kenilworth, NJ, USA. The authors acknowledge the database administration by Torsten Tille, Dresden, and the project administration of Mrs Romy Hoppenz and Mrs Linda Kottke at GWT-TUD GmbH, Dresden. Medical writing services provided by Richard Murphy PhD of Adelphi Communications Ltd, Macclesfield, UK were funded by Bayer AG in accordance with Good Publication Practice (GPP3) guidelines. The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Prof Marius M. Hoeper reports personal fees from Bayer AG, during the conduct of the study; personal fees from Actelion, personal fees from Acceleron, personal fees from MSD, personal fees from Jansen, personal fees from Pfizer, outside the submitted work. Dr Hans Klose reports speaker and consultancy fees from Actelion, Bayer AG, GSK, Novartis, Pfizer, and United Therapeutics and research support from Actelion, Bayer AG, GSK, Pfizer, and MSD. Dr Michael Halank reports personal fees and non-financial support from Actelion, AstraZeneca, Bayer AG, Berlin-Chemie, GSK, OMT, MSD, and Novartis. Dr George Giannakoulas reports speaker and consultancy fees from Actelion, Bayer, ELPEN Pharmaceuticals, GSK, Pfizer, Lilly, and United Therapeutics, and research support from GSK, ELPEN Pharmaceuticals, and Galenica. Dr Henning Gall has received honoraria and/or other support from Actelion, AstraZeneca, Bayer, BMS, GSK, Janssen-Cilag, Lilly, MSD, Novartis, OMT, Pfizer, and United Therapeutics. Dr Pavel Jansa reports consultancy and speaker fees from MSD, AOP Orphan, and Actelion. Prof Ekkehard Grünig reports research grants and speaker honoraria/consultancy fees from Actelion and Bayer/MSD, research grants from GSK, United Therapeutics, Bellerophon, OMT GmbH, Pfizer, Reata, and Novartis, and speaker honoraria from Bial, Medscape, and OrPha Swiss GmbH. Prof David Pittrow reports personal fees from Actelion, Bayer AG, Aspen, Boehringer Ingelheim, Sanofi, Biogen, Shire, and MSD outside the submitted work. Silvia Ulrich reports research grants and personal fees from Actelion, Bayer, MSD, and Orpha Swiss. Tobias J. Lange has received personal fees from Actelion, MSD, Pfizer, and OMT orphan. Dr Iraklis Tsangaris reports speaker and consultancy fees from Actelion, Bayer AG, ELPEN, GSK, MSD, Pfizer, and United Therapeutics. Stephan Rosenkranz reports remunerations for lectures and/or consultancy from Abbott, Actelion, Arena, Bayer, Ferrer, GSK, MSD, Novartis, Pfizer, and United Therapeutics; and research support to his institution from Actelion, Bayer, Novartis, Pfizer, and United Therapeutics. Repke J. Snijder reports grants from Pfizer and Actelion Pharmaceuticals. Prof Iveta Šimková reports consultancy and speaker fees from MSD, AOP Orphan, and Actelion. Dr Marc Humbert reports grants and personal fees from Bayer and GSK, and personal fees from Actelion, Merck, and United Therapeutics. Marion Delcroix has received investigator, speaker, consultant, and steering committee member fees from Actelion, Bayer AG, Bellerophon, Eli Lilly, GlaxoSmithKline, MSD, Pfizer, and Reata, and research grants from Actelion. Joan A. Barberà reports receipt of honoraria for consultation or speaker fees from Actelion and Merck; and research support through his institution from Actelion, Merck, GlaxoSmithKline, and Ferrer. Joanna Pepke-Zaba reports research grants and speaker honoraria/consultancy fees from Actelion, Bayer/MSD, and GSK. Jean-Luc Vachiéry reports ongoing consultancies to Actelion, Sonnivie, Arena Pharma, Bial Portela, and Respira Therapeutics, past consultancies to AstraZeneca, BayerShering, CardioMEMS, GlaxoSmithKline, Pfizer, Merck, and United Therapeutics, and current membership of an advisory board or similar group for Actelion and GlaxoSmithKline. Jean-Luc Vachiéry's institution receives funding from Actelion Pharmaceuticals for performing clinical studies. Regina Steringer-Mascherbauer, Jens Klotsche, and Miguel-Angel Gomez Sanchez have no conflicts of interest relevant to the EXPERT study. Hossein-Ardeschir Ghofrani reports personal fees for advisory board work, and payment for lectures including service on speaker bureaus, from Actelion, Bayer, GSK, Novartis, and Pfizer; consultancy fees from Actelion, Bayer, Bellerophon Pulse Technologies, GSK, MSD, Novartis, and Pfizer; and grants from Deutsche Forschungsgemeinschaft (DFG). Pilar Escribano Subias reports personal fees from Actelion, Bayer AG, GlaxoSmithKline, and Merck Sharp & Dohme, and grants from Actelion, Bayer AG, GlaxoSmithKline, and Ferrer, outside the submitted work. Gérald Simonneau reports personal fees and non-financial support from Actelion, personal fees and non-financial support from Bayer, personal fees and non-financial support from MSD, outside the submitted work. Douglas S. Helmersen reports industry-sponsored research with Bayer AG, United Therapeutics, and Gilead Sciences, Inc., and advisory board/speaker fees from Bayer AG and Actelion. David Langleben reports honoraria, consultation fees, research support, and/or travel expenses from Actelion, Arena, Bayer AG, Northern Therapeutics, PhaseBio, Acceleron, Janssen, and United Therapeutics. Anco Boonstra reports consultancy fees from Pfizer BV and hospitality from Teva Nederland. Lisa M. Mielniczuk reports speaker fees and honoraria from Bayer AG, and speaker fees, consultancy fees, and travel fees from Actelion. Evgenia Williams and Christian Meier are employees of Bayer AG.

Background: Atrial fibrillation (AF) may occur prior to or early in the course of acute pulmonary embolism (PE). The impact of AF on outcomes of patients with PE remains uncertain. Methods: Using the data from a large prospective multicenter registry of patients with objectively-confirmed PE (04/2014 to 01/2020), we identified three patient groups: 1) those with pre-existing AF 2) patients with newly identified AF within 2 days from the index PE (incident AF) and 3) patients without AF. We assessed the 90-day and 1-year risk of mortality and stroke in patients with AF, in unadjusted and multivariable adjusted models considering those without AF as referent. Results: Among 16,497 patients with PE, 792 had pre-existing AF. Compared with those without AF, patients with pre-existing AF, had increased odds of 90-day all-cause (Odds ratio [OR]: 2.81 (95% confidence interval [CI]: 2.33-3.38) and PE-related mortality (OR: 2.38, 95% CI: 1.37-4.14). After multivariable adjustment, pre-existing AF significantly increased the odds of all-cause mortality (OR: 1.91, 95% CI: 1.57-2.32) but not PE-related mortality (OR: 1.50; 95% CI: 0.85-2.66). Pre-existing AF was associated with increased hazard for ischemic stroke at 1-year follow-up (hazard ratio [HR]: 5.48; 95% CI: 3.10-9.69). Among 16,497 patients with PE, 445 developed incident AF within 2 days of acute PE. Incident AF was associated with increased odds of 90-day all-cause (OR: 2.28; 95% CI: 1.75-2.97) and PE-related (OR: 3.64; 95% CI: 2.01-6.59) mortality. Findings were similar in multivariable analyses and at 1-year follow-up (Figure). No patients with incident AF developed ischemic stroke. Conclusion: In patients with acute symptomatic PE, both pre-existing AF and incident AF predict an adverse clinical course, although the type of adverse outcomes may be different depending on the timing of AF onset.