Symptom-related screening programme for early detection of chronic thromboembolic pulmonary hypertension after acute pulmonary embolism: the SYSPPE study.

BACKGROUND: Chronic thromboembolic pulmonary hypertension (CTEPH) is the most severe long-term complication of acute pulmonary embolism (PE). We aimed to evaluate the impact of a symptom screening programme to detect CTEPH in PE survivors. METHODS: This was a multicentre cohort study of patients diagnosed with acute symptomatic PE between January 2017 and December 2018 in 16 centres in Spain. Patients were contacted by phone 2 years after the index PE diagnosis. Those with dyspnoea corresponding to a New York Heart Association (NYHA)/WHO scale≥II, visited the outpatient clinic for echocardiography and further diagnostic tests including right heart catheterisation (RHC). The primary outcome was the new diagnosis of CTEPH confirmed by RHC. RESULTS: Out of 1077 patients with acute PE, 646 were included in the symptom screening. At 2 years, 21.8% (n=141) reported dyspnoea NYHA/WHO scale≥II. Before symptom screening protocol, five patients were diagnosed with CTEPH following routine care. In patients with NYHA/WHO scale≥II, after symptom screening protocol, the echocardiographic probability of pulmonary hypertension (PH) was low, intermediate and high in 76.6% (n=95), 21.8% (n=27) and 1.6% (n=2), respectively. After performing additional diagnostic test in the latter 2 groups, 12 additional CTEPH cases were confirmed. CONCLUSIONS: The implementation of this simple strategy based on symptom evaluation by phone diagnosed more than doubled the number of CTEPH cases. Dedicated follow-up algorithms for PE survivors help diagnosing CTEPH earlier. TRIAL REGISTRATION NUMBER: NCT03953560.

Optimisation of detecting chronic thromboembolic pulmonary hypertension in acute pulmonary embolism survivors: the InShape IV study.

INTRODUCTION: Chronic thromboembolic pulmonary hypertension (CTEPH) is often diagnosed late in acute pulmonary embolism (PE) survivors: more efficient testing to expedite diagnosis may considerably improve patient outcomes. The InShape II algorithm safely rules out CTEPH (failure rate 0.29%) while requiring echocardiography in only 19% of patients but may be improved by adding detailed reading of the computed tomography pulmonary angiography (CTPA) diagnosing the index PE. METHODS: Twelve new algorithms, incorporating the CTEPH prediction score, ECG reading, NT-proBNP levels and dedicated CTPA reading were evaluated in the international InShape II (n=341) and part of the German FOCUS cohort (n=171). Evaluation criteria included failure rate, defined as the incidence of confirmed CTEPH in PE patients in whom echocardiography was deemed unnecessary by the algorithm, and the overall net reclassification index (NRI) compared to the InShape II algorithm. RESULTS: The algorithm starting with CTPA reading of the index PE for 6 signs of CTEPH, followed by the ECG/NTproBNP assessment and echocardiography resulted in the most beneficial change compared to InShape II with a need for echocardiography in 20% (+5%), a failure rate of 0%, and an NRI of +3.5, reflecting improved performance over the InShape II algorithm. In the FOCUS cohort, this approach lowered echocardiography need to 24% (-6%) and missed no CTEPH cases, with an NRI of +6.0. CONCLUSION: Dedicated CTPA reading of the index PE improved the performance of the InShape II algorithm and may improve the selection of PE survivors who require echocardiography to rule out CTEPH.

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.

COVID-19-Associated Pulmonary Embolism: Review of the Pathophysiology, Epidemiology, Prevention, Diagnosis, and Treatment.

COVID-19 is associated with endothelial activation in the setting of a potent inflammatory reaction and a hypercoagulable state. The end result of this thromboinflammatory state is an excess in thrombotic events, in particular venous thromboembolism. Pulmonary embolism (PE) has been of special interest in patients with COVID-19 given its association with respiratory deterioration, increased risk of intensive care unit admission, and prolonged hospital stay. The pathophysiology and clinical characteristics of COVID-19-associated PE may differ from the conventional non-COVID-19-associated PE. In addition to embolic events from deep vein thrombi, in situ pulmonary thrombosis, particularly in smaller vascular beds, may be relevant in patients with COVID-19. Appropriate prevention of thrombotic events in COVID-19 has therefore become of critical interest. Several changes in viral biology, vaccination, and treatment management during the pandemic may have resulted in changes in incidence trends. This review provides an overview of the pathophysiology, epidemiology, clinical characteristics, and risk factors of COVID-19-associated PE. Furthermore, we briefly summarize the results from randomized controlled trials of preventive antithrombotic therapies in COVID-19, focusing on their findings related to PE. We discuss the acute treatment of COVID-19-associated PE, which is substantially similar to the management of conventional non-COVID-19 PE. Ultimately, we comment on the current knowledge gaps in the evidence and the future directions in the treatment and follow-up of COVID-19-associated PE, including long-term management, and its possible association with long-COVID.

Epidemiology of Lung Cancer Mortality in Spain: Updated Information (1982-2021) and Predictions up to 2046.

BACKGROUND: Patterns of lung cancer (LC) mortality are important for planning health services and resource management. OBJECTIVES: We aimed to provide updated information (1982-2021) and project (LC) mortality rates in Spain (2022-2046). METHOD: We analysed data from the Spanish National Statistics Institute about mortality in LC (1982-2021), and we made predictions for the period 2022-2046. RESULTS: In 2021, a total of 22,413 people died of LC, and for the period 2042-2046, the projected annual average was 25,549 deaths. In males, age-standardised mortality rates (ASMR) (overall) after an initial period of increase (1982-1996, 2.2%) declined until 2021 (-1.4% per year), and this decline is expected to continue in the future (-1.9% per year during the period 2022-2046), although the projected decline is slightly higher (-2.0% during the period 2022-2046). In men, ASMR (all ages) after an initial period of increase (1982-1996, 2.2%) declined until 2021 (-1.4% per year), and this decline is expected to continue in the future during the period 2022-2046. In women, both the overall and truncated rates (35-64) increase during the period 1982-2021 (4.1% and 6.0% per year, respectively), and projected rates showed that both will decrease during the period 2022-2046, although more markedly in the truncated rates (-1.9% per year) than in the overall rates (-0.5% per year). CONCLUSIONS: Our projections show the magnitude of a steady upward trend in LC mortality among women in Spain that appears to be beginning to reverse from the current decade (similar to that observed for incidence).

Optimal follow-up after acute pulmonary embolism: a position paper of the European Society of Cardiology Working Group on Pulmonary Circulation and Right Ventricular Function, in collaboration with the European Society of Cardiology Working Group on Atherosclerosis and Vascular Biology, endorsed by the European Respiratory Society.

This position paper provides a comprehensive guide for optimal follow-up of patients with acute pulmonary embolism (PE), covering multiple relevant aspects of patient counselling. It serves as a practical guide to treating patients with acute PE complementary to the formal 2019 European Society of Cardiology guidelines developed with the European Respiratory Society. We propose a holistic approach considering the whole spectrum of serious adverse events that patients with acute PE may encounter on the short and long run. We underline the relevance of assessment of modifiable risk factors for bleeding, of acquired thrombophilia and limited cancer screening (unprovoked PE) as well as a dedicated surveillance for the potential development of chronic thromboembolic pulmonary hypertension as part of routine practice; routine testing for genetic thrombophilia should be avoided. We advocate the use of outcome measures for functional outcome and quality of life to quantify the impact of the PE diagnosis and identify patients with the post-PE syndrome early. Counselling patients on maintaining a healthy lifestyle mitigates the risk of the post-PE syndrome and improves cardiovascular prognosis. Therefore, we consider it important to discuss when and how to resume sporting activities soon after diagnosing PE. Additional patient-relevant topics that require Focused counselling are travel and birth control.

Low-molecular-weight heparin beyond 12 months in patients with cancer-associated thrombosis.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

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.

Major bleeding in patients with pulmonary embolism presenting with syncope.

INTRODUCTION: Syncope has been shown to be a risk factor of bleeding in patients receiving thrombolytic therapy for acute pulmonary embolism (PE). Whether syncope predicts bleeding in a broader population of patients with PE remains unknown. METHODS: We used the RIETE registry data to assess whether initial presentation with syncope could predict bleeding in PE patients receiving anticoagulant therapy, and to explore the association between presence of syncope and timing and site of major bleeding events. RESULTS: Among 45,765 patients with acute PE from March 2001 to January 2021, 6760 (14.8%) had syncope. Patients with syncope were older and more likely to have hypotension, tachycardia, hypoxaemia or elevated troponin levels than those without syncope. They also were more likely to receive thrombolytics. During the first 90 days, 1097 patients (2.4%) suffered major bleeding (gastrointestinal 335, hematoma 271 and intracranial 163) and 3611 died (158 had fatal bleeding). Patients with syncope had a higher rate of major bleeding (odds ratio [OR]: 1.63; 95% CI: 1.41-1.89) and a nonsignificantly higher rate of fatal bleeding (OR: 1.47; 95% CI: 0.99-2.17) than those without syncope. Multivariable analysis confirmed that patients with syncope were at increased risk for major bleeding (adjusted hazard ratio [aHR]: 1.34; 95% CI: 1.15-1.55). On sensitivity analysis, the increased risk for major bleeding was confirmed in patients initially receiving anticoagulant therapy without thrombolytics at 7 days (aHR: 1.47; 95% CI: 1.13-1.91) and 90 days (aHR: 1.33; 95%CI: 1.13-1.56). DISCUSSION: Syncope is a predictor of major bleeding events in patients with PE, even among those receiving anticoagulation monotherapy.

Adjusted D-dimer cutoff levels to rule out pulmonary embolism in patients hospitalized for COPD exacerbation: results from the SLICE trial.

BACKGROUND: For patients with suspected pulmonary embolism (PE), age- or clinically-adjusted D-dimer threshold level can be used to define a negative test that safely excludes PE and reduces the use of imaging. However, the utility of this approach in patients hospitalized for chronic obstructive pulmonary disease (COPD) exacerbation is undefined. METHODS: We ran an analysis of the patients hospitalized for COPD exacerbation and randomized to the intervention in the SLICE trial. Using the conventional strategy as the reference, we compared the proportion of patients with a negative D-dimer result, and the negative predictive value and sensitivity of three D-dimer threshold strategies for initial PE or subsequent diagnosis of venous thromboembolism (VTE): the age-adjusted strategy, the Wells-adjusted strategy, and the YEARS-adjusted strategy. RESULTS: We included 368 patients. Using a conventional threshold, 182 (49.5%) patients had negative D-dimer values, of whom 1 (0.6%) had PE (sensitivity, 94.1%). The use of an age-adjusted threshold increased the number of patients in whom PE could be excluded from 182 to 233 patients (63.3%), and the proportion of false-negative findings increased from 0.5% to 1.7% (sensitivity, 76.5%). With the use of the Wells or YEARS strategies, 64.4% and 71.5% had negative values, and the proportion of false-negative findings was 2.5% (sensitivity, 64.7%) and 2.7% (sensitivity, 58.8%), respectively. CONCLUSIONS: In patients hospitalized for COPD exacerbation, compared with the conventional strategy, age- or clinically-adjusted strategies of D-dimer interpretation were associated with a larger proportion of patients in whom PE was ruled out with a higher failure rate. TRIAL REGISTRATION: ClinicalTrials.gov number: NCT02238639 .

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.

Derivation and validation of a clinical prediction rule for thrombolysis-associated major bleeding in patients with acute pulmonary embolism: the BACS score.

BACKGROUND: Improved prediction of the risk of major bleeding in patients with acute pulmonary embolism (PE) receiving systemic thrombolysis is crucial to guide the choice of therapy. METHODS: The study included consecutive patients with acute PE who received systemic thrombolysis in the RIETE registry. We used multivariable logistic regression analysis to create a risk score to predict 30-day major bleeding episodes. We externally validated the risk score in patients from the COMMAND VTE registry. We also compared the newly created risk score against the Kuijer and RIETE scores. RESULTS: Multivariable logistic regression identified four predictors for major bleeding: recent major Bleeding (3 points), Age >75 years (1 point), active Cancer (1 point), and Syncope (1 point) (BACS). Among 1172 patients receiving thrombolytic therapy in RIETE, 446 (38%) were classified as having low-risk (none of the variables present, 0 points) of major bleeding according to the BACS score, and the overall 30-day major bleeding rate of this group was 2.9% (95% CI, 1.6-4.9%), compared with 44% (95% CI, 14-79%) in the high-risk group (>3 points). In the validation cohort, 51% (149/290) of patients were classified as having low-risk, and the overall 30-day major bleeding rate of this group was 1.3%. In RIETE, the 30-day major bleeding event rates in the Kuijer and RIETE low-risk stratum were 5.3% and 4.4%, respectively. CONCLUSIONS: The BACS score is an easily applicable aid for prediction of the risk of major bleeding in the population of PE patients who receive systemic thrombolysis.

D-dimer and high-sensitivity C-reactive protein levels to predict venous thromboembolism recurrence after discontinuation of anticoagulation for cancer-associated thrombosis.

BACKGROUND: Optimal duration of anticoagulation for cancer-associated thrombosis (CAT) remains unclear. This study assessed D-dimer (DD) and high-sensitivity C-reactive protein (hs-CRP) levels after the withdrawal of anticoagulation treatment to predict the risk of venous thromboembolism (VTE) recurrence among patients with CAT. METHODS: Prospective, multicentre study to evaluate CAT with ≥3 months of anticoagulation that was subsequently discontinued. Blood samples were taken when patients stopped the anticoagulation and 21 days later to determine the DD and hs-CRP levels. All patients were followed up for 6 months to detect VTE recurrence. RESULTS: Between 2013 and 2015, 325 patients were evaluated and 114 patients were ultimately enrolled in the study. The mean age was 62 ± 14 years and nearly 40% had metastasis. Ten patients developed VTE recurrence within 6 months (8.8%, 95% confidence interval [CI]: 4.3-15.5%). The DD and hs-CRP levels after 21 days were associated with VTE recurrence. The subdistribution hazard ratios were 9.82 for hs-CRP (95% CI: 19-52) and 5.81 for DD (95% CI: 1.1-31.7). CONCLUSIONS: This study identified that hs-CRP and DD were potential biomarkers of VTE recurrence after discontinuation of anticoagulation in CAT. A risk-adapted strategy could identify low-risk patients who may benefit from discontinuation of anticoagulation.

Management appropriateness and outcomes of patients with acute pulmonary embolism.

The impact of adherence to published guidelines on the outcomes of patients with acute pulmonary embolism (PE) has not been well defined by previous studies.In this prospective cohort study of patients admitted to a respiratory department (n=2096), we evaluated whether patients with PE had better outcomes if they were acutely managed according to international guidelines. Outcomes consisted of all-cause mortality, PE-related mortality, recurrent venous thromboembolism (VTE) and major bleeding events during the first month of follow-up after diagnosis.Overall, 408 patients (19% (95% CI 18-21%)) did not receive guideline-adherent PE management. Patients receiving non-adherent management were significantly more likely to experience all-cause mortality (adjusted odds ratio (OR) 2.39 (95% CI 1.57-3.61) or PE-related mortality (adjusted OR 5.02 (95% CI 2.42-10.42); p<0.001) during follow-up. Non-adherent management was also a significant independent predictor of recurrent VTE (OR 2.19 (95% CI 1.11-4.32); p=0.03) and major bleeding (OR 2.65 (95% CI 1.66-4.24); p<0.001). An external validation cohort of 34 380 patients with PE from the RIETE registry confirmed these findings.PE management that does not adhere to guidelines for indications related to anticoagulation, thrombolytics and inferior vena cava filters is associated with worse patient outcomes.

Screening for Occult Cancer in Patients With Unprovoked Venous Thromboembolism: A Systematic Review and Meta-analysis of Individual Patient Data.

BACKGROUND: Screening for cancer in patients with unprovoked venous thromboembolism (VTE) often is considered, but clinicians need precise data on cancer prevalence, risk factors, and the effect of different types of screening strategies. PURPOSE: To estimate the prevalence of occult cancer in patients with unprovoked VTE, including in subgroups of different ages or those that have had different types of screening. DATA SOURCES: MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials up to 19 January 2016. STUDY SELECTION: Prospective studies evaluating cancer screening strategies in adults with unprovoked VTE that began enrolling patients after 1 January 2000 and had at least 12 months of follow-up. DATA EXTRACTION: 2 investigators independently reviewed abstracts and full-text articles and independently assessed risk of bias. DATA SYNTHESIS: 10 eligible studies were identified. Individual data were obtained for all 2316 patients. Mean age was 60 years; 58% of patients received extensive screening. The 12-month period prevalence of cancer after VTE diagnosis was 5.2% (95% CI, 4.1% to 6.5%). The point prevalence of cancer was higher in patients who had extensive screening than in those who had more limited screening initially (odds ratio [OR], 2.0 [CI, 1.2 to 3.4]) but not at 12 months (OR, 1.4 [CI, 0.89 to 2.1]). Cancer prevalence increased linearly with age and was 7-fold higher in patients aged 50 years or older than in younger patients (OR, 7.1 [CI, 3.1 to 16]). LIMITATION: Variation in patient characteristics and extensive screening strategies; unavailability of long-term mortality data. CONCLUSION: Occult cancer is detected in 1 in 20 patients within a year of receiving a diagnosis of unprovoked VTE. Older age is associated with a higher cancer prevalence. Although an extensive screening strategy initially may detect more cancer cases than limited screening, whether this translates into improved patient outcomes remains unclear. PRIMARY FUNDING SOURCE: None. (PROSPERO: CRD42016033371).

Noninvasive ventilation for severely acidotic patients in respiratory intermediate care units : Precision medicine in intermediate care units.

BACKGROUND: Severe acidosis can cause noninvasive ventilation (NIV) failure in chronic obstructive pulmonary disease (COPD) patients with acute hypercapnic respiratory failure (AHRF). NIV is therefore contraindicated outside of intensive care units (ICUs) in these patients. Less is known about NIV failure in patients with acute cardiogenic pulmonary edema (ACPE) and obesity hypoventilation syndrome (OHS). Therefore, the objective of the present study was to compare NIV failure rates between patients with severe and non-severe acidosis admitted to a respiratory intermediate care unit (RICU) with AHRF resulting from ACPE, COPD or OHS. METHODS: We prospectively included acidotic patients admitted to seven RICUs, where they were provided NIV as an initial ventilatory support measure. The clinical characteristics, pH evolutions, hospitalization or RICU stay durations and NIV failure rates were compared between patients with a pH ≥ 7.25 and a pH < 7.25. Logistic regression analysis was performed to determine the independent risk factors contributing to NIV failure. RESULTS: We included 969 patients (240 with ACPE, 540 with COPD and 189 with OHS). The baseline rates of severe acidosis were similar among the groups (45 % in the ACPE group, 41 % in the COPD group, and 38 % in the OHS group). Most of the patients with severe acidosis had increased disease severity compared with those with non-severe acidosis: the APACHE II scores were 21 ± 7.2 and 19 ± 5.8 for the ACPE patients (p < 0.05), 20 ± 5.7 and 19 ± 5.1 for the COPD patients (p < 0.01) and 18 ± 5.9 and 17 ± 4.7 for the OHS patients, respectively (NS). The patients with severe acidosis also exhibited worse arterial blood gas parameters: the PaCO2 levels were 87 ± 22 and 70 ± 15 in the ACPE patients (p < 0.001), 87 ± 21 and 76 ± 14 in the COPD patients, and 83 ± 17 and 74 ± 14 in the OHS patients (NS)., respectively Further, the patients with severe acidosis required a longer duration to achieve pH normalization than those with non-severe acidosis (patients with a normalized pH after the first hour: ACPE, 8 % vs. 43 %, p < 0.001; COPD, 11 % vs. 43 %, p < 0.001; and OHS, 13 % vs. 51 %, p < 0.001), and they had longer RICU stays, particularly those in the COPD group (ACPE, 4 ± 3.1 vs. 3.6 ± 2.5, NS; COPD, 5.1 ± 3 vs. 3.6 ± 2.1, p < 0.001; and OHS, 4.3 ± 2.6 vs. 3.7 ± 3.2, NS). The NIV failure rates were similar between the patients with severe and non-severe acidosis in the three disease groups (ACPE, 16 % vs. 12 %; COPD, 7 % vs. 7 %; and OHS, 11 % vs. 4 %). No common predictive factor for NIV failure was identified among the groups. CONCLUSIONS: ACPE, COPD and OHS patients with AHRF and severe acidosis (pH ≤ 7.25) who are admitted to an RICU can be successfully treated with NIV in these units. These results may be used to determine precise RICU admission criteria.

Short-term clinical outcome of normotensive patients with acute PE and high plasma lactate.

BACKGROUND: Strategies for identifying normotensive patients with acute symptomatic PE at high risk of PE-related complications remain to be defined. METHODS: This prospective cohort study aimed to determine the role of plasma lactate levels in the risk assessment of normotensive patients with acute PE. Outcomes assessed over the 7 days after the diagnosis of PE included PE-related mortality and haemodynamic collapse, defined as need for cardiopulmonary resuscitation, systolic blood pressure <90 mm Hg for at least 15 min, need for catecholamine administration, or need for mechanical ventilation. RESULTS: Between December 2012 and January 2014, the study enrolled 496 normotensive outpatients with acute symptomatic PE. PE-related complications occurred in 20 (4.0%; 95% CI 2.5% to 6.2%) of the 496 patients. These patients had higher baseline lactate levels (median 2.66 mmol/L; IQR 1.56-5.96 mmol/L) than patients without complications (1.20 mmol/L; IQR 1.20-2.00 mmol/L) (p<0.001). Overall, 135 patients (27.2%) had plasma lactate ≥2 mmol/L. Fourteen (10.4%) of them had PE-related complications versus 6 of 361 patients with low lactate (negative predictive value 98.3%; p<0.001). Patients with elevated plasma lactate had an increased rate of PE-related complications (adjusted OR 5.3; 95% CI 1.9 to 14.4; p=0.001) compared with those with low lactate. The combination of elevated plasma lactate with markers of right ventricular dysfunction (by echocardiogram) and myocardial injury (by cardiac troponin) was a particularly useful prognostic indicator (positive predictive value 17.9%; 95% CI 6.1% to 36.9%). CONCLUSIONS: Plasma lactate represents a powerful predictor of short-term PE-related complications and may provide guidance for decision-making in PE care.

C-reactive Protein and Risk of Right Ventricular Dysfunction and Mortality in Patients With Acute Symptomatic Pulmonary Embolism.

BACKGROUND: Right ventricle (RV) dysfunction increases the risk of death from pulmonary embolism (PE). C-reactive protein (CRP) might identify RV inflammation and dysfunction in patients with PE. METHODS: This cohort study enrolled consecutive stable patients with acute PE between 2017 and 2023. We stratified patients by quartiles of CRP. We evaluated the association between CRP quartiles and the presence of RV dysfunction, and used multivariable models to assess for an association between CRP and the outcomes of all-cause and PE-specific mortality during the 30 days of follow-up after PE diagnosis. RESULTS: The study included 633 stable patients with PE. Patients without RV dysfunction had significantly lower median (IQR) CRP levels compared with patients with RV dysfunction (n=509, 31.7 [10.0-76.4]mg/L vs n=124, 45.4 [16.0-111.4]mg/L; P=0.018). CRP showed a statistically significant positive association with the presence of RV dysfunction (P<0.01). On multivariable analysis, CRP level was not significantly associated with 30-day all-cause mortality (adjusted odds ratio [OR] per mg/L increment, 1.00; 95% CI, 1.00-1.01; P=0.095), but higher CRP was associated with significantly higher PE-related mortality (adjusted OR, 1.01; 95% CI, 1.00-1.01; P=0.026). Compared with patients in CRP quartile 1, patients in quartiles 2, 3, and 4 had a stepwise increase in the adjusted odds of 30-day all-cause death of 2.41 (P=0.148), 3.04 (P=0.062), and 3.15 (P=0.052), respectively. CONCLUSIONS: As an indicator of RV dysfunction, CRP may improve risk stratification algorithms for hemodynamically stable patients with acute symptomatic PE.

Oxygen Therapy in Patients With Intermediate-Risk Acute Pulmonary Embolism: A Randomized Trial.

BACKGROUND: The effect of supplemental oxygen therapy in patients with intermediate-risk pulmonary embolism (PE) who do not have hypoxemia at baseline is uncertain. RESEARCH QUESTION: Does supplemental oxygen improve echocardiographic parameters in nonhypoxemic patients with intermediate-risk PE? STUDY DESIGN AND METHODS: This pilot trial randomly assigned nonhypoxemic patients with stable PE and echocardiographic right ventricle (RV) enlargement to receive anticoagulation plus supplemental oxygen for the first 48 h vs anticoagulation alone. The primary outcome was normal echocardiographic RV size 48 h after randomization. Secondary efficacy outcomes were the numerical change in the RV to left ventricle (LV) diameter ratio measured 48 h and 7 days after randomization with respect to the baseline ratio measured at inclusion. RESULTS: The study was stopped prematurely because of the COVID-19 pandemic after recruiting 70 patients (mean ± SD age, 67.3 ± 16.1 years; 36 female [51.4%]) with primary outcome data. Forty-eight h after randomization, normalization of the RV size occurred in 14 of the 33 patients (42.4%) assigned to oxygen and in eight of the 37 patients (21.6%) assigned to ambient air (P = .08). In the oxygen group, the mean RV to LV ratio was reduced from 1.28 ± 0.28 at baseline to 1.01 ± 0.16 at 48 h (P < .001); in the ambient air group, mean RV to LV ratios were 1.21 ± 0.18 at baseline and 1.08 ± 0.19 at 48 h (P < .01). At 90 days, one major bleeding event and one death (both in the ambient air group) had occurred. INTERPRETATION: In analyses limited by a small number of enrollees, compared with ambient air, supplemental oxygen did not significantly increase the proportion of patients with nonhypoxemic intermediate-risk PE whose RV to LV ratio normalized after 48 h of treatment. This pilot trial showed improvement in some ancillary efficacy outcomes and provides support for a definitive clinical outcomes trial. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT04003116; URL: www. CLINICALTRIALS: gov.