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.

Nocturnal hypoxemia and prognosis in patients with acute symptomatic pulmonary embolism.

BACKGROUND: Nocturnal hypoxemia has been associated with cardiovascular and non-cardiovascular morbidity and mortality. This study aimed to investigate the prognostic value of nocturnal hypoxemia among patients with hemodynamically stable acute symptomatic pulmonary embolism (PE). METHODS: We performed an ad hoc secondary analysis of clinical data from a prospective cohort study. Nocturnal hypoxemia was measured by the percent sleep registry with oxygen saturation <90% [TSat90]). Outcomes assessed over the 30-days after the diagnosis of PE included PE-related death, other cardiovascular deaths, clinical deterioration requiring an escalation of treatment, recurrent venous thromboembolism (VTE), acute myocardial infarction [AMI], or stroke. RESULTS: Of the 221 hemodynamically stable patients with acute PE from which the TSat90 could be calculated and did not receive supplemental oxygen, the primary outcome occurred in 11 (5.0%; 95% confidence interval [CI], 2.5% to 8.7%) within 30-days after the diagnosis of PE. When categorized by quartiles, TSat90 was not significantly associated with the occurrence of the primary outcome in unadjusted Cox regression analysis (hazard ratio, 0.96; 95% CI, 0.57 to 1.63; P = 0.88), or after adjustment for body mass index (adjusted hazard ratio, 0.97; 95% CI, 0.57 to 1.65; P = 0.92). When examined as a completely continuous variable (between 0 and 100), TSat90 was not associated with a significant increase in the adjusted hazard of 30-day primary outcome rates (hazard ratio, 0.97; 95% CI, 0.86 to 1.10; P = 0.66). CONCLUSIONS: In this study, nocturnal hypoxemia did not identify stable patients with acute symptomatic PE at increased risk for adverse cardiovascular events.

National Early Warning Score-2 for Identification of Patients with Intermediate-High-Risk Pulmonary Embolism.

Consensus statements have proposed the use of the National Early Warning Score 2 (NEWS2) to identify stable patients with acute pulmonary embolism (PE) and an intermediate-high risk of adverse outcomes. We aimed to externally validate NEWS2 and compare it to another predictive score (Bova). Using NEWS2 (cutoff ≥5 and ≥7) and the Bova score (cutoff >4), we classified patients as intermediate-high risk (vs. non-intermediate-high risk), and we compared the test characteristics of these risk classification tools for a complicated course within 30 days after PE diagnosis. We also assessed the validity of NEWS2 for predicting a complicated course by adding the results of echocardiography and troponin testing to the model. Of the 848 enrolled patients, the NEWS2 score ≥5 classified 471 (55.5%) and the Bova score classified 37 (4.4%) as intermediate-high risk. NEWS2 had a significantly lower specificity for a 30-day complicated course than Bova (45.4 vs. 96.3%, respectively; p < 0.001). Using the higher score threshold (≥7), the NEWS2 classified 99 (11.7%) as intermediate-high risk, and the specificity was 88.9% (difference with Bova, 7.4%; p < 0.001). The proportion of patients with intermediate-high risk PE was 2.4% for the combination of a positive troponin testing and echocardiographic right ventricle dysfunction and a positive NEWS2 (score ≥7), while the specificity was 97.8% (difference with Bova, 1.5%; p = 0.07). Bova outperforms NEWS2 for predicting a complicated course among stable patients with PE. Addition of troponin testing and echocardiography improved the specificity of NEWS2, although it was not superior to Bova. CLINICALTRIALS.GOV NUMBER: : NCT02238639.

Usefulness of the National Early Warning Score for Risk Stratification of Stable Patients With Acute Symptomatic Pulmonary Embolism

Objectives: The aim of this study was to assess the performance of the National Early Warning Score 2 (NEWS2) in predicting a short-term complicated outcome in stable patients with acute symptomatic pulmonary embolism (PE). We also studied the ability of the NEWS2 score compared with the simplified Pulmonary Embolism Severity Index (sPESI) for identifying low-risk patients with acute PE. Methods: We performed a retrospective analysis of a prospective cohort composed of 848 patients with acute PE. The NEWS2 and the sPESI were calculated for each patient according to different clinical variables. We assessed the predictive accuracy of these scores for a 30-day complicated outcome using the C statistic, which was obtained by logistic regression models and ROC curves. We also assessed the test and performance characteristics of the low-risk versus high-risk categories of each prediction rule. Results: Overall, 63 out of 848 patients died (7.4%; 95% confidence interval, 5.7%-9.2%) during the first month of follow-up. Both scores showed a similarly poor predictive value for 30-day complicated outcome (C statistic, 0.68 and 0.62). The sPESI classified fewer patients as low-risk (36.9% versus 44.5%; P<0.01). Compared with the NEWS2 score, the sPESI showed significantly higher sensitivity (92.1% versus 66.7%) and a better negative predictive value (98.4% versus 94.4%). Conclusion: Both scores provide similar information for stratifying the risk of a complicated outcome in stable patients with PE. The sPESI identified low-risk patients with PE better than the NEWS2 score. (AU)

Usefulness of the National Early Warning Score for Risk Stratification of Stable Patients With Acute Symptomatic Pulmonary Embolism.

OBJECTIVES: The aim of this study was to assess the performance of the National Early Warning Score 2 (NEWS2) in predicting a short-term complicated outcome in stable patients with acute symptomatic pulmonary embolism (PE). We also studied the ability of the NEWS2 score compared with the simplified Pulmonary Embolism Severity Index (sPESI) for identifying low-risk patients with acute PE. METHODS: We performed a retrospective analysis of a prospective cohort composed of 848 patients with acute PE. The NEWS2 and the sPESI were calculated for each patient according to different clinical variables. We assessed the predictive accuracy of these scores for a 30-day complicated outcome using the C statistic, which was obtained by logistic regression models and ROC curves. We also assessed the test and performance characteristics of the low-risk versus high-risk categories of each prediction rule. RESULTS: Overall, 63 out of 848 patients died (7.4%; 95% confidence interval, 5.7%-9.2%) during the first month of follow-up. Both scores showed a similarly poor predictive value for 30-day complicated outcome (C statistic, 0.68 and 0.62). The sPESI classified fewer patients as low-risk (36.9% versus 44.5%; P<0.01). Compared with the NEWS2 score, the sPESI showed significantly higher sensitivity (92.1% versus 66.7%) and a better negative predictive value (98.4% versus 94.4%). CONCLUSION: Both scores provide similar information for stratifying the risk of a complicated outcome in stable patients with PE. The sPESI identified low-risk patients with PE better than the NEWS2 score.

Comparison of various prognostic scores for identification of patients with intermediate-high risk pulmonary embolism.

BACKGROUND: Various risk assessment tools have been proposed to identify stable patients with acute pulmonary embolism (PE) who are at high risk of early adverse outcome (i.e., intermediate-high risk). METHODS: We evaluated the ability of the 2019 ESC, Bova, modified FAST and PEITHO-3 models for predicting a 30-day complicated course (death, haemodynamic collapse, and/or recurrent PE) in a cohort of 848 stable patients with acute PE. We also tested whether replacement of echocardiographic right ventricle (RV) dysfunction by computed tomographic (CT) RV enlargement provides comparable prognostic information for identifying these patients. RESULTS: A complicated course occurred in 63 (7.4 %) of the 848 patients with PE during the first month of follow-up. The proportion of patients designated as having intermediate-high risk PE was 6.7 % with the ESC model, 4.4 % with the Bova score, 15.7 % with the FAST score, and 5.2 % with the PEITHO-3 model. However, among patients identified as intermediate-high risk, the 30-day complicated course rate was higher with the Bova score (21.6 %) than with the ESC model (17.5 %), the PEITHO-3 model (15.9 %), or the modified FAST score (14.3 %). When echocardiographic RV dysfunction was replaced by CT RV enlargement in the models, the proportion of patients classified as having intermediate-high risk PE and the rate of an adverse outcome among them slightly increased. CONCLUSIONS: The Bova score might identify patients with intermediate-high risk PE slightly better than the ESC, PEITHO-3, and modified FAST score. When echocardiography is not readily available, CT-assessed RV enlargement might be used for identifying intermediate-high risk PE. CLINICALTRIALS: gov number: NCT02238639.

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.

Untreated obstructive sleep apnea and cardiovascular outcomes in patients with acute symptomatic pulmonary embolism.

There is a paucity of data examining the prognostic significance of untreated obstructive sleep apnea (OSA) in hemodynamically stable patients with acute pulmonary embolism (PE). This prospective cohort study enrolled consecutive non-hypotensive patients with acute PE who underwent an overnight sleep study within 48 h after diagnosis. The patients were divided into 2 groups based on apnea-hypopnea index (AHI): OSA (AHI ≥15) and non-OSA (AHI <15) groups. The study used a composite of fatal or nonfatal cardiovascular events, including PE-related death, other cardiovascular deaths, clinical deterioration requiring an escalation of treatment, recurrent venous thromboembolism, acute myocardial infarction, or stroke within 30-days after the diagnosis of PE as the primary outcome. Between January 1, 2018, and December 31, 2020, 283 eligible patients were prospectively enrolled in 2 academic hospitals, of whom 268 patients completed a sleep study within 7 days of PE diagnosis. OSA was found in 47% (95% confidence interval [CI], 41 to 54%) of patients. The primary outcome occurred in 13 (4.9%) patients within 30-days after the diagnosis of PE. The crude incidence of the composite was not significantly different in the OSA than the non-OSA group (30-day estimate, 6.3% versus 3.5%; P = 0.30). OSA did not significantly predict the incidence of the primary outcome after adjustment for age, sex, body mass index, systolic blood pressure, heart rate, and oxygen saturation (adjusted hazard ratio, 2.15; 95% confidence interval, 0.67-6.87). In this study, untreated OSA was not a significant multivariable predictor of adverse cardiovascular events in patients with acute PE.

Prognostic Significance of Findings on CTPA Supporting an Alternative Diagnosis to PE Among Patients Hospitalized for an Exacerbation of COPD: Predefined Subanalysis of the SLICE Trial. / Significado pronóstico de los diagnósticos alternativos a la TEP hallados en la tomografía computarizada de tórax de pacientes ingresados por agudización de EPOC: subanálisis predefinido del ensayo SLICE.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Significado pronóstico de los diagnósticos alternativos a la TEP hallados en la tomografía computarizada de tórax de pacientes ingresados por agudización de EPOC: subanálisis predefinido del ensayo SLICE / Prognostic Significance of Findings on CTPA Supporting an Alternative Diagnosis to PE Among Patients Hospitalized for an Exacerbation of COPD: Predefined Subanalysis of the SLICE Trial

Antecedentes: El ensayo clínico SLICE no demostró un beneficio clínico de la búsqueda activa de la tromboembolia de pulmón (TEP) en pacientes que requirieron ingreso por agudización de su EPOC. El objetivo de este subanálisis fue determinar la frecuencia y el significado pronóstico del hallazgo de un diagnóstico alternativo a la TEP en la tomografía computarizada de tórax (TC) realizada a pacientes hospitalizados por EPOC agudizada. Métodos: Analizamos los pacientes del grupo intervención de SLICE que recibieron una TC con resultado negativo para TEP. Evaluamos mediante el uso de regresión logística multivariable la asociación entre un diagnóstico alternativo y el evento primario compuesto de reingreso por EPOC y la mortalidad por cualquier causa en los primeros 90 días después de la aleatorización. Resultados: Este análisis incluyó a 175 pacientes del grupo intervención que recibieron una TC con un resultado negativo para TEP. De ellos, 84 (48,0%) fueron diagnosticados de infección bronquial aguda, 13 (7,4%) de cáncer de pulmón, 10 (5,7%) de insuficiencia cardiaca, 8 (4,6%) de neumonía, 18 (10,3%) de otros diagnósticos, y en 42 (24,0%) pacientes la TC fue normal. En el análisis multivariable, un diagnóstico alternativo no se asoció de manera significativa con el evento primario (odds ratio: 0,64; IC 95%: 0,30-1,38; P=0,26). Conclusiones: Entre los pacientes que requieren ingreso por agudización de EPOC, la TC ofrece un diagnóstico alternativo a la TEP en el 76% de las ocasiones. El tratamiento específico de estas patologías no se asocia a un mejor pronóstico durante el seguimiento. (AU)

Background: 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. Methods: 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. Results: 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). Conclusions: 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. (AU)

[Translated article] Prognostic Significance of Findings on CTPA Supporting an Alternative Diagnosis to PE Among Patients Hospitalized for an Exacerbation of COPD: Predefined Subanalysis of the SLICE Trial / Significado pronóstico de los diagnósticos alternativos a la TEP hallados en la tomografía computarizada de tórax de pacientes ingresados por agudización de EPOC: subanálisis predefinido del ensayo SLICE

Background: 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. Methods: 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. Results: 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). Conclusions: 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. (AU)

Antecedentes: El ensayo clínico SLICE no demostró un beneficio clínico de la búsqueda activa de la tromboembolia de pulmón (TEP) en pacientes que requirieron ingreso por agudización de su EPOC. El objetivo de este subanálisis fue determinar la frecuencia y el significado pronóstico del hallazgo de un diagnóstico alternativo a la TEP en la tomografía computarizada de tórax (TC) realizada a pacientes hospitalizados por EPOC agudizada. Métodos: Analizamos los pacientes del grupo intervención de SLICE que recibieron una TC con resultado negativo para TEP. Evaluamos mediante el uso de regresión logística multivariable la asociación entre un diagnóstico alternativo y el evento primario compuesto de reingreso por EPOC y la mortalidad por cualquier causa en los primeros 90 días después de la aleatorización. Resultados: Este análisis incluyó a 175 pacientes del grupo intervención que recibieron una TC con un resultado negativo para TEP. De ellos, 84 (48,0%) fueron diagnosticados de infección bronquial aguda, 13 (7,4%) de cáncer de pulmón, 10 (5,7%) de insuficiencia cardiaca, 8 (4,6%) de neumonía, 18 (10,3%) de otros diagnósticos, y en 42 (24,0%) pacientes la TC fue normal. En el análisis multivariable, un diagnóstico alternativo no se asoció de manera significativa con el evento primario (odds ratio: 0,64; IC 95%: 0,30-1,38; P=0,26). Conclusiones: Entre los pacientes que requieren ingreso por agudización de EPOC, la TC ofrece un diagnóstico alternativo a la TEP en el 76% de las ocasiones. El tratamiento específico de estas patologías no se asocia a un mejor pronóstico durante el seguimiento. (AU)