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.

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 .

Shock score for prediction of clinical outcomes among stable patients with acute symptomatic pulmonary embolism.

BACKGROUND: The Composite Pulmonary Embolism Shock (CPES) score has been developed to identify normotensive patients with acute pulmonary embolism (PE) and a low cardiac index (referred to as normotensive shock). We aimed to externally assess the validity of this model for predicting a complicated course among hemodynamically stable patients with acute PE. METHODS: Using prospectively collected data from the PROgnosTic valuE of Computed Tomography scan (PROTECT) study, we calculated the CPES score for each patient and the proportion of patients with a score > 3. We calculated the test performance characteristics to predict a complicated course (i.e., death from any cause, hemodynamic collapse, or recurrent PE) and the discriminatory power using the area under the receiver operating characteristic curve. RESULTS: Sixty-three of the 848 (7.4 %) patients had a complicated course during the 30-day follow-up period. Of the 848 enrolled patients, the CPES score was positive (i.e., score > 3) in 78 (9.2 %). The specificity was 92.1 % (723/785), the positive predictive value was 20.5 % (16/78), and the positive likelihood ratio was 3.22 for a complicated course. The areas under the receiver operating characteristic curve for a complicated course were 0.71 (95 % confidence interval [CI], 0.65-0.78). With the higher score risk classification threshold (cutoff score > 4), the proportion of patients designated as positive was 2.1 %, and the specificity was 98.1 %. When echocardiographic right ventricle (RV) dysfunction was replaced by computed tomographic RV enlargement, the specificity was 85.4 %, the positive predictive value was 14.2 %, and the positive likelihood ratio was 2.06 for a complicated course. When analyses were restricted to the subgroup of patients with intermediate-risk PE, the specificity and the positive predictive value for a complicated course were identical to the overall cohort. CONCLUSIONS: The CPES score has acceptable C-statistic, excellent specificity, and low positive predictive value for identification of hemodynamic deterioration in normotensive patients with PE. CLINICALTRIALS: gov number: NCT02238639.

High-Sensitivity vs Conventional Troponin Cutoffs for Risk Stratification in Patients With Acute Pulmonary Embolism.

Importance: High-sensitivity troponin tests can detect even milder cardiac troponin elevations in plasma, beyond the threshold of conventional troponin tests. Whether detection of low-grade cardiac troponin elevation is associated with outcomes of patients with hemodynamically stable pulmonary embolism (PE) and helps with risk stratification is unknown. Objective: To determine the association between high-sensitivity cardiac troponin I (hs-cTnI) compared with conventional cardiac troponin I (cTnI) and PE risk designations according to the European Society of Cardiology (ESC) 2019 classification scheme and clinical outcomes in patients with hemodynamically stable PE. Design, Setting, and Participants: This is a post hoc analysis of data from the prospective Prognostic Value of Computed Tomography (PROTECT) multicenter cohort study enrolling patients from 12 hospital emergency departments in Spain. In this analysis, cTnI and hs-cTnI were compared with respect to ESC risk designation, and the association between troponin values and a complicated course after PE diagnosis was evaluated. Of 848 patients enrolled in PROTECT, 834 (98.3%) had hsTnI and cTnI values available and were included in the present analysis. Data were analyzed from May to December 2022. Exposures: Troponin blood testing with cTnI (threshold of >0.05 ng/mL) vs hs-cTnI (threshold of >0.029 ng/mL) assays at the time of PE diagnosis. Main Outcomes: Complicated course, defined as hemodynamic collapse, recurrent PE, or all-cause death, within 30 days after PE. Results: Of 834 patients (mean [SEM] age, 67.5 [0.6] years; 424 [50.8%] female), 139 (16.7%) had elevated cTnI and 264 (31.7%) elevated hs-TnI, respectively. During follow-up, 62 patients (7.4%; 95% CI, 5.7-9.4) had a complicated course. Analyzing troponin elevation as a binary variable, elevated cTnI (odds ratio [OR], 2.84; 95% CI, 1.62-4.98) but not hs-cTnI (OR, 1.12; 95% CI, 0.65-1.93) was associated with increased odds of a complicated course. Of 125 patients who had elevated hs-cTnI but normal cTnI, none (0; 95% CI, 0.0-2.9) developed a complicated course. Using the 2019 ESC risk stratification scheme, hs-TnI classified fewer patients as low risk compared with cTnI. Among 78 patients designated as ESC low risk when using cTnI but not with hsTnI, none (0; 95% CI, 0.0-4.6) had a complicated course. Conclusions and Relevance: In this study of patients with hemodynamically stable PE, hs-cTnI identified modest elevations in cardiac troponin levels. However, the results did not provide additive clinical value compared with cTnI. These findings suggest that use of hs-cTnI may result in overestimation of the risk in patients with stable PE.

STOP-Bang questionnaire in patients hospitalized with acute symptomatic pulmonary embolism.

STUDY OBJECTIVES: The STOP-Bang questionnaire is a validated screening tool for obstructive sleep apnea (OSA). We conducted this study to validate it among patients hospitalized with acute symptomatic pulmonary embolism (PE). METHODS: This prospective cohort study enrolled consecutive stable patients with acute PE who underwent an overnight sleep study within 7 days after diagnosis. Our outcomes were: i) the STOP-Bang questionnaire's utility for risk stratification, ii) the discrimination of the STOP-Bang questionnaire categories, iii) the false negative rate of STOP-Bang questionnaire prediction, and iv) the clinical utility of the STOP-Bang questionnaire to exclude OSA. We also calculated the test performance characteristics to predict OSA. RESULTS: During the study period, 268 patients completed a sleep study. OSA was found in 47% of patients. OSA incidence in low-, moderate-, and high-risk STOP-Bang groups was 22.4%, 48.2%, and 61.5%, respectively (P <0.001). The area under the receiver operating characteristics curve of the STOP-Bang questionnaire for risk of OSA was 0.65. The false negative rate of a low-risk STOP-Bang questionnaire result to rule out OSA was 22.4% and the clinical utility was 21.6%. The sensitivity was 89.8% (97.2% for men and 80.4% for women). CONCLUSIONS: The STOP-Bang questionnaire showed poor discrimination for the risk of OSA in hospitalized patients with acute symptomatic PE. It had a high false negative rate and a low clinical utility. The STOP-Bang questionnaire had a good sensitivity in men, and might be used to rule out OSA in this population.

Chronic thromboembolic pulmonary hypertension treatment and sex: Systematic review and meta-analysis.

BACKGROUND AND OBJECTIVES: Chronic thromboembolic pulmonary hypertension (CTEPH) is a complication of pulmonary embolism and a major cause of chronic pulmonary hypertension leading to right heart failure and death. While pulmonary endarterectomy is the treatment of choice, some patients might benefit from medical therapy or balloon pulmonary angioplasty. Sex differences in outcomes of these therapies are not well characterized. MATERIAL AND METHODS: We conducted a systematic review and meta-analysis to investigate sex differences in outcomes of various therapies for CTEPH. We searched MEDLINE, PubMed, Embase, CINAHL and the Cochrane Library databases between January 1, 2010 and April 30, 2021, published in English. We pooled incidence estimates using random-effects meta-analyses. We evaluated heterogeneity using the I2 statistic. We assessed publication bias using Begg's and Egger's tests. This study is registered in PROSPERO, CRD42021268504. RESULTS: A total of 19 studies met the eligibility criteria, but only 3 trials provided separate outcomes for women and men. Two studies evaluated the efficacy of BPA, and one study evaluated the efficacy of riociguat (129 patients). Overall, 57.3% of patients were women and 62.6% were in functional class III. Mean time of follow-up was 55.5 (SD 26.1) weeks. Women showed a significantly better response in cardiac index (mean difference [MD], 0.10L/min/m2; 95% confidence interval [CI], 0.04-0.16; I2=0%; P=0.001). Alternatively, the reduction of pulmonary vascular resistances was significantly higher for men than for women (MD, 161.17dynscm-5; 95% CI, 67.99-254.35; I2=0%; P=0.0007). CONCLUSIONS: Women and men might show different hemodynamic responses to riociguat or BPA for CTEPH.

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.

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)