The rationale, design, and methods of a trial to evaluate the efficacy and safety of oxygen therapy in patients with intermediate-risk acute pulmonary embolism.

BACKGROUND: In patients with intermediate-risk pulmonary embolism (PE), reversal of hypoxic vasoconstriction could constitute a target for treatment that protects the right ventricular (RV) function until endogenous fibrinolysis occurs. The Air vs oxygen for Intermediate-Risk pulmonary embolism (AIR) trial aims to assess the effect of oxygen therapy in patients with intermediate-risk acute PE who do not have hypoxemia at baseline. METHODS AND ANALYSES: AIR is a prospective, multicenter, randomized, open-label, parallel-group, proof-of-concept trial. A total of 90 patients hospitalized with intermediate-risk PE and an oxygen saturation of 90% or higher at baseline will be randomized in a 1:1 fashion to receive supplemental oxygen or ambient air. The primary outcome is a RV/LV diameter ratio equal or less than 1.0 on echocardiography measured 48 hours after the start of treatment. Secondary efficacy outcomes are the numerical change in the ratio of the RV to the LV diameter measured 48 hours and 7 days after the start of treatment, with respect to the baseline ratio measured at randomization. Clinical adverse events will be also collected. RESULTS: Enrollment started in July 2019 and is expected to proceed until 2022. Median age of the first 50 patients was 74 years (interquartile range, 61-81), and 50% were female. CONCLUSIONS: This multicenter trial will provide information about the value of supplemental oxygen in patients with intermediate-risk acute PE who do not have hypoxemia at baseline. The results will contribute to research that may assist patients with intermediate-risk PE in the future.

Cancer Histology and Natural History of Patients with Lung Cancer and Venous Thromboembolism.

Background: In patients with lung cancer and venous thromboembolism (VTE), the influence of cancer histology on outcome has not been consistently evaluated. Methods: We used the RIETE registry (Registro Informatizado Enfermedad TromboEmbólica) to compare the clinical characteristics and outcomes during anticoagulation in patients with lung cancer and VTE, according to the histology of lung cancer. Results: As of April 2022, there were 482 patients with lung cancer and VTE: adenocarcinoma 293 (61%), squamous 98 (20%), small-cell 44 (9.1%), other 47 (9.8%). The index VTE was diagnosed later in patients with squamous cancer than in those with adenocarcinoma (median, 5 vs. 2 months). In 50% of patients with adenocarcinoma, the VTE appeared within the first 90 days since cancer diagnosis. During anticoagulation (median 106 days, IQR: 45-214), 14 patients developed VTE recurrences, 15 suffered major bleeding, and 218 died: fatal pulmonary embolism 10, fatal bleeding 2. The rate of VTE recurrences was higher than the rate of major bleeding in patients with adenocarcinoma (11 vs. 6 events), and lower in those with other cancer types (3 vs. 9 events). On multivariable analysis, patients with adenocarcinoma had a non-significantly higher risk for VTE recurrences (hazard ratio [HR]: 3.79; 95%CI: 0.76-18.8), a lower risk of major bleeding (HR: 0.29; 95%CI: 0.09-0.95), and a similar risk of mortality (HR: 1.02; 95%CI: 0.76-1.36) than patients with other types of lung cancer. Conclusions: In patients with lung adenocarcinoma, the rate of VTE recurrences outweighed the rate of major bleeding. In patients with other lung cancers, it was the opposite.

Effect of Prognostic Guided Management of Patients With Acute Pulmonary Embolism According to the European Society of Cardiology Risk Stratification Model.

Background: A recent trial showed that management driven by prognostic assessment was effective in reducing the length of stay (LOS) for acute stable pulmonary embolism (PE). The efficacy and safety of this strategy in each subgroup of risk stratification remains unknown. Methods: We conducted a post-hoc analysis of the randomized IPEP study to evaluate the effect of a management strategy guided by early use of a prognostic pathway in the low- and intermediate-high risk subgroups defined by the European Society of Cardiology (ESC) model. These subgroups were retrospectively identified in the control arm. The primary outcome was LOS. The secondary outcomes were 30-day clinical outcomes. Results: Of 249 patients assigned to the intervention group, 60 (24%) were classified as low-, and 30 (12%) as intermediate-high risk. Among 249 patients assigned to the control group, 66 (27%) were low-, and 13 (5%) intermediate-high risk. In the low-risk group, the mean LOS was 2.1 (±0.9) days in the intervention group and 5.3 (±2.9) days in the control group (P < 0.001). In this group, no significant differences were observed in 30-day readmissions (0% vs. 3.0%, respectively), all-cause (0% vs. 0%) and PE-related mortality rates (0% vs. 0%), or severe adverse events (0% vs. 1.5%). In the intermediate-high risk group, the mean LOS was 5.3 (±1.8) days in the intervention group and 6.5 (±2.5) days in the control group (P = 0.08). In this group, no significant differences were observed in 30-day readmissions (3.3% vs. 3.0%, respectively), all-cause (6.7% vs. 7.7%) and PE-related mortality rates (6.7% vs. 7.7%), or severe adverse events (16.7% vs. 15.4%). Conclusion: The use of a prognostic assessment and management pathway was effective in reducing the LOS for acute PE without comprising safety across subgroups of risk stratification. Clinical Trial Registration: [ClinicalTrials.gov], Identifier [NCT02733198].

Anticoagulant therapy for splanchnic vein thrombosis: an individual patient data meta-analysis.

Robust evidence on the optimal management of splanchnic vein thrombosis (SVT) is lacking. We conducted an individual-patient meta-analysis to evaluate the effectiveness and safety of anticoagulation for SVT. Medline, Embase, and clincaltrials.gov were searched up to June 2021 for prospective cohorts or randomized clinical trials including patients with SVT. Data from individual datasets were merged, and any discrepancy with published data was resolved by contacting study authors. Three studies of a total of 1635 patients were included. Eighty-five percent of patients received anticoagulation for a median duration of 316 days (range, 1-730 days). Overall, incidence rates for recurrent venous thromboembolism (VTE), major bleeding, and mortality were 5.3 per 100 patient-years (p-y; 95% confidence interval [CI], 5.1-5.5), 4.4 per 100 p-y (95% CI, 4.2-4.6), and 13.0 per 100 p-y (95% CI, 12.4-13.6), respectively. The incidence rates of all outcomes were lower during anticoagulation and higher after treatment discontinuation or when anticoagulation was not administered. In multivariable analysis, anticoagulant treatment appeared to be associated with a lower risk of recurrent VTE (hazard ratio [HR], 0.42; 95% CI, 0.27-0.64), major bleeding (HR, 0.47; 95% CI, 0.30-0.74), and mortality (HR, 0.23; 95% CI, 0.17-0.31). Results were consistent in patients with cirrhosis, solid cancers, myeloproliferative neoplasms, unprovoked SVT, and SVT associated with transient or persistent nonmalignant risk factors. In patients with SVT, the risk of recurrent VTE and major bleeding is substantial. Anticoagulant treatment is associated with reduced risk of both outcomes.

Heart Rate and Mortality in Patients With Acute Symptomatic Pulmonary Embolism.

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.

Randomised controlled trial of a prognostic assessment and management pathway to reduce the length of hospital stay in normotensive patients with acute pulmonary embolism.

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<0.001). The mean total cost of prognostic tests was EUR 174.76 in the intervention group, compared with EUR 233.12 in the control group (mean difference EUR -58.37, 95% CI EUR -84.34- to -32.40). The mean total hospitalisation cost per patient was EUR 2085.66 in the intervention group, compared with EUR 3232.97 in the control group (mean difference EUR -1147.31, 95% CI EUR -1414.97- to -879.65). No significant differences were observed in 30-day readmission (4.0% versus 4.8%), all-cause mortality (2.4% versus 2.0%) or PE-related mortality (0.8% versus 1.2%) rates. CONCLUSIONS: The use of a prognostic assessment and management pathway was effective in reducing the LOS for acute PE.

[Thrombotic Risk and Covid-19: Review of Current Evidence for a Better Diagnostic and Therapeutic Approach]. / Riesgo trombótico y COVID-19: revisión de la evidencia actual para una mejor aproximación diagnóstica y terapéutica.

The new SARS-CoV-2 coronavirus has created an unprecedented global health problem, resulting in more than 250,000 confirmed deaths. The disease produced by this virus, called Covid-19, presents with variable clinical manifestations, from practically asymptomatic patients with catarrhal processes to severe pneumonias that rapidly evolve to acute respiratory distress syndrome (ARDS) and multiorgan failure. In recent weeks, papers have been published describing coagulation disorders and arterial and venous thrombotic complications in these patients, mainly among those admitted to intensive care units. The infection triggers an immune response, which causes different inflammatory mediators to be released into the blood. These include cytokines, which interact with platelets and different coagulation proteins, and promote thrombogenesis. One of the most widely studied coagulation markers in Covid-19 is D-dimer (DD), raised levels of which have prognostic implications, although the best cut-off point for the diagnosis of venous thromboembolism (VTE) in this population has not been clarified, nor has its usefulness in determining the intensity of thromboprophylaxis required in these patients. Until sufficiently robust information (preferably from well-designed clinical trials) is available, the recommendations of clinical practice guidelines for the prophylaxis, diagnosis and treatment of VTE should be followed in Covid-19 patients.

Effect of a Pulmonary Embolism Diagnostic Strategy on Clinical Outcomes in Patients Hospitalized for COPD Exacerbation: A Randomized Clinical Trial.

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.

Hipertensión pulmonar tromboembólica crónica en España: una década de cambio / Chronic thromboembolic pulmonary hypertension in Spain: a decade of change

Introducción y objetivos El tratamiento de la hipertensión pulmonar tromboembólica crónica (HTPTEC) ha evolucionado en la última década. Sin embargo, apenas se dispone de información sobre el impacto de estos logros en la población general a escala nacional. Este estudio se diseñó para describir las características de los pacientes con HTPTEC en España en la última década. Métodos Se recogieron prospectivamente datos epidemiológicos, clínicos y pronósticos de los pacientes con HTPTEC consecutivos incluidos en el registro español REHAP desde el 1 de enero de 2007 al 31 de diciembre de 2018. Se evaluaron las diferencias entre diferentes periodos de tiempo, estableciendo 2013 como fecha de referencia para el análisis. Se calculó la puntuación de propensión para la intervención mediante un modelo multivariable de regresión logística. Resultados Se incluyó a 1.019 pacientes; se remitió a 659 (64,4%) a un centro nacional de referencia en HTPTEC. Del total, se seleccionó a 350 (34,3%) para cirugía y a 97 (9,6%) para tratamiento percutáneo. Entre los pacientes diagnosticados entre 2007 y 2012 hubo más frecuencia de muerte que entre los diagnosticados de 2013 en adelante (HR=1,83; IC95%, 1,07-3,15; p=0,027). En el grupo de pacientes ajustado por el modelo de puntuación de propensión, las resistencias vasculares pulmonares basales y la distancia recorrida en el test de 6 min de marcha también fueron determinantes del pronóstico (respectivamente, HR=1,24; IC95%, 1,15-1,33; p=0,011, y HR=0,93; IC95%, 0,90-0,97; p=0,001). Las tasas de supervivencia de los pacientes que se sometieron a un procedimiento intervencionista (trombendarterectomía pulmonar o angioplastia con balón de arterias pulmonares) resultaron llamativamente altas. Conclusiones Durante la última década, el diagnóstico y el pronóstico de la HTPTEC han mejorado de manera considerable. La gravedad de la enfermedad al diagnóstico determinó el perfil de riesgo. ... (AU)

Introduction and objectives Chronic thromboembolic pulmonary hypertension (CTEPH) treatment has evolved in the last decade. However, there is scarce information on the long-term impact of this progress in a real-life population at a national level. This study was designed to analyze the characteristics of CTEPH patients in Spain over the last decade. Methods We prospectively collected epidemiological, clinical, and prognostic data from CTEPH patients consecutively included in the Spanish REHAP registry from January 1, 2007, to December 31, 2018. We evaluated differences over time, establishing 2013 as the reference date for analysis. Propensity scores for interventional treatment were calculated using a multivariable logistic regression model. Results A total of 1019 patients were included; 659 (64.4%) were evaluated at a national CTEPH center. Overall, 350 patients (34.3%) were selected for surgery and 97 (9.6%) for percutaneous treatment. Patients diagnosed between 2007 and 2012 died more frequently than those diagnosed from 2013 onward (HR, 1.83; 95%CI, 1.07-3.15; P=.027). Within the subgroup of patients adjusted by propensity score, baseline pulmonary vascular resistance and the 6-minute walk test distance also determined the outcome (HR, 1.24; 95%CI, 1.15-1.33; P=.011; and HR, 0.93; 95%CI, 0.90-0.97; P=.001, respectively). High survival rates were found in patients who underwent an invasive procedure (pulmonary endarterectomy or balloon pulmonary angioplasty). Conclusions CTEPH diagnosis and prognosis have consistently improved in the last decade. Baseline disease severity determines the risk profile. Patients who undergo pulmonary endarterectomy or balloon pulmonary angioplasty have better outcomes. (AU)

Coagulation disorders and thromboembolic disease in COVID-19: review of current evidence in search of a better approach.

The new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been an unprecedented global health problem, causing more than 20 million infections and more than 900,000 deaths (September 2020). The SARS-CoV-2 infection, known as COVID-19, has various clinical presentations, from asymptomatic or mild catarrhal processes to severe pneumonia that rapidly progresses to acute respiratory distress syndrome (ARDS) and multiple organ failure. In the last few months, much scientific literature has been devoted to descriptions of different aspects of the coagulation disorders and arterial and venous thrombotic complications associated with COVID-19, particularly venous thromboembolism (VTE). These studies have revealed that SARS-CoV-2 could lead to a prothrombotic state reflecting the high cumulative incidence of associated thrombotic events, particularly in patients admitted to intensive care units (ICUs). As regards the coagulopathy observed in association with SARS-CoV-2 infection, the mechanisms that activate coagulation have been hypothesized as being linked to immune responses, through the release of pro-inflammatory mediators that interact with platelets, stimulate the expression of tissue factor, induce an upregulation of plasminogen activator inhibitor-1, suppress the fibrinolytic system and lead to endothelial dysfunction, triggering thrombogenesis. D-dimer elevation has been recognized as a useful biomarker of poor prognosis, although the best cut-off point for predicting VTE in COVID-19 patients has still not been clarified. This review will try to update all the available scientific information on this important topic with enormous clinical and therapeutic implications.

From Health-Related Quality of Life (HRQoL) of Patients with Pulmonary Hypertension to Patient Experience with the Care Received: Should We Be More Aware of Current Patient Needs?

INTRODUCTION: Self-perceived health-related quality of life (HRQoL) of patients with pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) and their experience with the care received are important for improving their management. We conducted a study to assess both patient-reported outcomes (PROs) and how they interrelate. METHODS: This was a cross-sectional, observational study of consecutive patients with PAH and CTEPH attending pulmonary hypertension (PH)-specialized units at 25 hospitals in Spain. PRO measurements used included CAMPHOR/EQ-5D-5L questionnaires (HRQoL) and IEXPAC (healthcare experience). Patient characteristics were collected. Relationships were analysed with Pearson's correlation coefficient and linear regression analyses. RESULTS: A total of 185 patients with PAH and 93 patients with CTEPH aged 54.4 ± 14.4 and 64.8 ± 13.4 years were included: 63.6% and 72% were functional class (FC) I-II; median time from diagnosis was 3 and 2 years, respectively. Most patients with PAH received combination oral therapy. CAMPHOR scores indicated moderate-to-high impairment in the "activity" scale (PAH 21.6 ± 6.8; CTEPH 21.0 ± 6.3). EQ-5D-5L index and visual analogue scale (VAS) score (PAH 0.59 ± 0.15 and 65.55 ± 21.54; CTEPH 0.59 ± 0.13 and 66.95 ± 18.71, respectively) indicated moderate HRQoL impairment. HRQoL was mostly affected by FC. IEXPAC scores (PAH 7.08 ± 1.56 and CTEPH 7.13 ± 1.61) indicated good healthcare experience. In patients with PAH, the CAMPHOR "symptom" and "QoL" domains inversely correlated with the IEXPAC "patient self-management" factor. CONCLUSION: In patients with long-standing PAH and CTEPH with good disease control, functional limitations greatly impact HRQoL while symptoms and generic QoL were less affected. Healthcare received was perceived as good; however, use of information and communication technologies, patient associations and promotion of self-management should improve for enhanced patient experience.

Venous thromboembolism in solid-organ transplant recipients: Findings from the RIETE registry.

BACKGROUND: Venous thromboembolism (VTE) represents a relevant cause of morbidity in patients with solid-organ transplant (SOT), but there are scarce data on the management and outcomes in these patients. METHODS: RIETE is a worldwide, ongoing observational registry of patients with objectively confirmed, acute VTE. We used the RIETE database to compare the clinical characteristics, treatment and outcomes in SOT recipients vs. non-recipients. RESULTS: From January 2001 to December 2019, 83,210 patients were enrolled in RIETE. Of these, 329 (0.4%) were SOT recipients: in the kidney 221, liver 41, lung 28 and heart 25. Median duration of anticoagulation was similar in SOT recipients and non-recipients (174 vs. 182 days). During anticoagulation, 1180 patients developed deep vein thrombosis (DVT) recurrences, 1028 pulmonary embolism (PE) recurrences, 2392 had major bleeding, 3119 non-major bleeding and 8157 died. SOT recipients had a higher rate of major bleeding (hazard ratio [HR]: 2.55; 95% CI: 1.62-3.84) and clinically relevant non-major bleeding (HR: 1.94; 95% CI: 1.23-2.93) than non-recipients, with no differences in the rates of DVT recurrences (HR: 0.96; 95% CI: 0.30-2.32), PE recurrences (HR: 1.11; 95% CI: 0.35-2.67) or death (HR: 0.98; 95% CI: 0.67-1.40). On multivariable analysis, only liver transplant recipients were at an increased risk for major bleeding compared to non-recipients (adjusted HR: 3.17; 95% CI: 1.02-9.87). CONCLUSIONS: Treatment of VTE in SOT recipients is associated with an increased risk of bleeding compared to non-recipients. This is mainly due to the influence of liver transplant recipients. In non-liver SOT recipients, the risk for bleeding was similar to that in non-recipients.

Incidence, risk factors, and thrombotic load of pulmonary embolism in patients hospitalized for COVID-19 infection.

OBJECTIVE: To determine the incidence, characteristics, and risk factors of pulmonary embolism (PE) among patients hospitalized for COVID-19. PATIENTS AND METHODS: We performed a prospective observational study of a randomly selected cohort of consecutive patients hospitalized for COVID-19 infection between March 8, 2020 through April 25, 2020. All eligible patients underwent a computed tomography pulmonary angiography independently of their PE clinical suspicion and were pre-screened for a baseline elevated D-dimer level. RESULTS: 119 patients were randomly selected from the 372 admitted to one tertiary hospital in Valencia (Spain) for COVID-19 infection during the period of study. Seventy-three patients fulfilled both the inclusion criteria and none of the exclusion criteria and were finally included in the study. Despite a high level of pharmacological thromboprophylaxis (89%), the incidence of PE was 35.6% (95% confidence interval [CI], 29.6 to 41.6%), mostly with a peripheral location and low thrombotic load (Qanadli score 18.5%). Multivariate analysis showed that heart rate (Hazard Ratio [HR], 1.04), room-air oxygen saturation (spO2) (HR, 0.87), D-dimer (HR, 1.02), and C-reactive protein (CRP) levels (HR, 1.01) at the time of admission were independent predictors of incident PE during hospitalization. A risk score was constructed with these four variables showing a high predictive value of incident PE (AUC-ROC: 0.86; 95% CI: 0.80 to 0.93). CONCLUSIONS: Our findings confirmed a high incidence of PE in hospitalized COVID-19 patients. Heart rate, spO2, D-dimer, and CRP levels at admission were associated with higher rates of PE during hospitalization.

Riesgo trombótico y COVID-19: revisión de la evidencia actual para una mejor aproximación diagnóstica y terapéutica / Thrombotic Risk and Covid-19: Review of Current Evidence for a Better Diagnostic and Therapeutic Approach

El nuevo coronavirus SARS-CoV-2 ha supuesto un problema sanitario mundial sin precedentes, y ha ocasionado más de 250.000 muertes confirmadas. La enfermedad producida por este virus, denominada COVID-19, cursa con presentaciones clínicas variables, desde cuadros paucisintomáticos y procesos catarrales hasta neumonías graves que evolucionan rápidamente a síndrome de distrés respiratorio agudo (SDRA) y fallo multiorgánico. En las últimas semanas se han publicado algunos trabajos que describen alteraciones de la coagulación y complicaciones trombóticas arteriales y venosas en estos pacientes, principalmente entre aquellos ingresados en unidades de cuidados intensivos. Las infecciones desencadenan una respuesta inmunitaria, que provoca la liberación de distintos mediadores inflamatorios a la sangre. Entre ellos se encuentran las citocinas, que interaccionan con las plaquetas y con distintas proteínas de la coagulación, y favorecen la trombogénesis. Uno de los marcadores de la coagulación más estudiados en la COVID-19 es el dímero D (DD), y su elevación tiene implicaciones pronósticas, aunque no se ha aclarado el mejor punto de corte para el diagnóstico de enfermedad tromboembólica venosa (ETEV) en esta población ni su utilidad para decidir la intensidad de la tromboprofilaxis para estos pacientes. Hasta disponer de información suficientemente robusta (preferentemente de ensayos clínicos bien diseñados), se deberían seguir las recomendaciones de las guías de práctica clínica para la profilaxis, diagnóstico y tratamiento de la ETEV en los pacientes COVID-19

The new SARS-CoV-2 coronavirus has created an unprecedented global health problem, resulting in more than 250,000 confirmed deaths. The disease produced by this virus, called Covid-19, presents with variable clinical manifestations, from practically asymptomatic patients with catarrhal processes to severe pneumonias that rapidly evolve to acute respiratory distress syndrome (ARDS) and multiorgan failure. In recent weeks, papers have been published describing coagulation disorders and arterial and venous thrombotic complications in these patients, mainly among those admitted to intensive care units. The infection triggers an immune response, which causes different inflammatory mediators to be released into the blood. These include cytokines, which interact with platelets and different coagulation proteins, and promote thrombogenesis. One of the most widely studied coagulation markers in Covid-19 is D-dimer (DD), raised levels of which have prognostic implications, although the best cut-off point for the diagnosis of venous thromboembolism (VTE) in this population has not been clarified, nor has its usefulness in determining the intensity of thromboprophylaxis required in these patients. Until sufficiently robust information (preferably from well-designed clinical trials) is available, the recommendations of clinical practice guidelines for the prophylaxis, diagnosis and treatment of VTE should be followed in Covid-19 patients

Portopulmonary hypertension: prognosis and management in the current treatment era - results from the REHAP registry.

BACKGROUND: Portopulmonary hypertension (PoPH) is a rare condition with poorer survival compared to idiopathic/familial pulmonary arterial hypertension (IPAH/FPAH). AIMS: To compare the characteristics, survival, prognostic factors and management of PoPH and IPAH/FPAH patients and to assess the impact of treatment on survival of PoPH patients. METHODS: Analysis of data of prevalent and incident PoPH patients enrolled in the Spanish registry of PAH (REHAP) from January 1998 to December 2017 and comparison with IPAH/FPAH patients. Variables analysed: patient and disease (PAH and liver) characteristics, first-line PAH-targeted therapy, causes of death, prognostic factors and survival (according to aetiology and treatment in PoPH patients). RESULTS: Compared to IPAH/FPAH patients (n = 678), patients with PoPH (n = 237) were predominantly men, older and had better functional class and higher prevalence of ascites. Haemodynamics were better. Biomarkers for heart failure were worse. Age- and sex-adjusted 5-year survival rate from diagnosis was 49.3% for PoPH patients and 68.7% for IPAH patients (P < 0.001). Treated PoPH had better survival than non-treated. PAH- and liver-related causes accounted for 30.2% and 24.7% of deaths in PoPH patients. PoPH patients were less likely to receive first-line PAH-targeted therapy and this was associated with greater mortality. Increasing age, worse exercise capacity and ascites were independent prognostic factors of poorer survival; first-line oral monotherapy was associated with improved survival. Eight (3.4%) PoPH patients underwent liver transplantation. CONCLUSIONS: PoPH patients are undertreated and show poorer survival than IPAH/FPAH patients. First-line treatment with PAH-targeted therapy was associated with better survival. Presence of ascites was a predictor of mortality.

Presenting Characteristics, Treatment Patterns, and Outcomes among Patients with Venous Thromboembolism during Hospitalization for COVID-19.

Venous thromboembolism (VTE) is common in patients with coronavirus disease-2019 (COVID-19). However, limited data exist on patient characteristics, treatments, and outcomes. To describe the clinical characteristics, treatment patterns, and short-term outcomes of patients diagnosed with VTE during hospitalization for COVID-19. This is a prospective multinational study of patients with incident VTE during the course of hospitalization for COVID-19. Data were obtained from the Registro Informatizado de la Enfermedad TromboEmbólica (RIETE) registry. All-cause mortality, VTE recurrences, and major bleeding during the first 10 days were separately investigated for patients in hospital wards versus those in intensive care units (ICUs). As of May 03, 2020, a total number of 455 patients were diagnosed with VTE (83% pulmonary embolism, 17% isolated deep vein thrombosis) during their hospital stay; 71% were male, the median age was 65 (interquartile range, 55-74) years. Most patients (68%) were hospitalized in medical wards, and 145 in ICUs. Three hundred and seventeen (88%; 95% confidence interval [CI]: 84-91%) patients were receiving thromboprophylaxis at the time of VTE diagnosis. Most patients (88%) received therapeutic low-molecular-weight heparin, and 15 (3.6%) received reperfusion therapies. Among 420 patients with complete 10-day follow-up, 51 (12%; 95% CI: 9.3-15%) died, no patient recurred, and 12 (2.9%; 95% CI: 1.6-4.8%) experienced major bleeding. The 10-day mortality rate was 9.1% (95% CI: 6.1-13%) among patients in hospital wards and 19% (95% CI: 13-26%) among those in ICUs. This study provides characteristics and early outcomes of patients diagnosed with acute VTE during hospitalization for COVID-19. Additional studies are needed to identify the optimal strategies to prevent VTE and to mitigate adverse outcomes associated.

Chronic thromboembolic pulmonary hypertension in Spain: a decade of change.

INTRODUCTION AND OBJECTIVES: Chronic thromboembolic pulmonary hypertension (CTEPH) treatment has evolved in the last decade. However, there is scarce information on the long-term impact of this progress in a real-life population at a national level. This study was designed to analyze the characteristics of CTEPH patients in Spain over the last decade. METHODS: We prospectively collected epidemiological, clinical, and prognostic data from CTEPH patients consecutively included in the Spanish REHAP registry from January 1, 2007, to December 31, 2018. We evaluated differences over time, establishing 2013 as the reference date for analysis. Propensity scores for interventional treatment were calculated using a multivariable logistic regression model. RESULTS: A total of 1019 patients were included; 659 (64.4%) were evaluated at a national CTEPH center. Overall, 350 patients (34.3%) were selected for surgery and 97 (9.6%) for percutaneous treatment. Patients diagnosed between 2007 and 2012 died more frequently than those diagnosed from 2013 onward (HR, 1.83; 95%CI, 1.07-3.15; P=.027). Within the subgroup of patients adjusted by propensity score, baseline pulmonary vascular resistance and the 6-minute walk test distance also determined the outcome (HR, 1.24; 95%CI, 1.15-1.33; P=.011; and HR, 0.93; 95%CI, 0.90-0.97; P=.001, respectively). High survival rates were found in patients who underwent an invasive procedure (pulmonary endarterectomy or balloon pulmonary angioplasty). CONCLUSIONS: CTEPH diagnosis and prognosis have consistently improved in the last decade. Baseline disease severity determines the risk profile. Patients who undergo pulmonary endarterectomy or balloon pulmonary angioplasty have better outcomes.

Rivaroxaban or apixaban in fragile patients with acute venous thromboembolism.

INTRODUCTION: The efficacy and safety of the direct oral anticoagulants (DOACs) in fragile patients (age ≥ 75 years and/or creatinine clearance [CrCl] levels ≤50 mL/min and/or body weight ≤50kg) with venous thromboembolism (VTE) have not been consistently compared. MATERIAL AND METHODS: We used the RIETE database to compare the rates of the composite of VTE recurrences or major bleeding during anticoagulation in fragile patients with VTE, according to the use of rivaroxaban or apixaban for initial and long-term therapy. RESULTS: From January 2013 to October 2019, 36,889 patients were recruited, of whom 14,831 (40%) were fragile. Overall, 999 fragile patients (15%) received DOACs starting within the first 48 h: rivaroxaban 711 and apixaban 288. Median duration of therapy was: 113 vs. 111 days. A substantial amount of patients in both subgroups (25% vs. 40%) received non-recommended doses of DOACs. During anticoagulation, 13 patients developed VTE recurrences, 18 had major bleeding and 36 died. When only considering patients receiving recommended doses (n = 705), there were no differences between drugs in the rate of the composite outcome (rate ratio [RR]: 1.08; 95%CI: 0.35-3.30) or all-cause death (RR: 0.99; 95%CI: 0.32-3.08). On multivariable analysis, patients receiving rivaroxaban or apixaban at recommended doses had a similar risk for the composite outcome (hazard ratio: 1.34; 95%CI: 0.35-5.06). CONCLUSION: The use of rivaroxaban or apixaban at recommended doses in fragile patients with VTE was associated with a similar risk for VTE recurrences or major bleeding.