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Assessment of right ventricular function in acute pulmonary embolism
Assessment of right ventricular function in acute pulmonary embolism Deisy Barrios, Raquel Morillo, Jos´e Luis Lobo, Rosa Nieto, Ana Jaureguizar, Ana K. Portillo, Esther Barbero, Covadonga Fernandez-Golfin, Roger D. Yusen, David Jim´enez PII: DOI: Reference:
S0002-8703(16)30290-3 doi: 10.1016/j.ahj.2016.12.009 YMHJ 5343
To appear in:
American Heart Journal
Received date: Accepted date:
27 July 2016 22 December 2016
Please cite this article as: Barrios Deisy, Morillo Raquel, Lobo Jos´e Luis, Nieto Rosa, Jaureguizar Ana, Portillo Ana K., Barbero Esther, Fernandez-Golfin Covadonga, Yusen Roger D., Jim´enez David, Assessment of right ventricular function in acute pulmonary embolism, American Heart Journal (2016), doi: 10.1016/j.ahj.2016.12.009
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
RV function in PE
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ASSESSMENT OF RIGHT VENTRICULAR FUNCTION IN ACUTE
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PULMONARY EMBOLISM
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Authors:
Deisy Barrios1, Raquel Morillo1, José Luis Lobo2, Rosa Nieto1, Ana
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Jaureguizar1, Ana K. Portillo3, Esther Barbero1, Covadonga Fernandez-Golfin4,
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Roger D. Yusen5, David Jiménez1, the PROTECT investigators
Affiliation: 1
Respiratory Department, Ramón y Cajal Hospital and Universidad de Alcalá IRYCIS,
Madrid, Spain 2
Respiratory Department, Hospital Universitario Araba, Álava, Spain
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Department of Internal Medicine, Ramón y Cajal Hospital and Instituto Ramón y Cajal
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de Investigación Sanitaria IRYCIS, Madrid, Spain. 4
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Cardiology Department, Ramón y Cajal Hospital and Instituto Ramón y Cajal de
Investigación Sanitaria IRYCIS, Madrid, Spain 5
Divisions of Pulmonary and Critical Care Medicine and General Medical Sciences,
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Washington University School of Medicine, St. Louis, Missouri, USA
Correspondence: David Jiménez
Respiratory Department and Medicine Department Ramón y Cajal Hospital, Universidad de Alcalá IRYCIS 28034 Madrid, Spain Phone: +34913368314 e-mail: [email protected]
Short title: Right ventricle function in PE Word count: 2,376
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HIGHLIGHTS
Multidetector computed tomography (MDCT) and transthoracic echocardiography agree in 53% of patients on the presence or absence of
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right ventricular (RV) overload.
Incorporation of echocardiographic right ventricular overload to the
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simplified PESI and MDCT does not improve identification of low-risk PE
The combination of MDCT and echocardiographic assessment of RV
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function might be required for identifying intermediate-high risk patients with
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PE.
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patients.
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ABSTRACT
Background: The optimal approach to assess right ventricular (RV) function in
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patients with acute symptomatic pulmonary embolism (PE) lacks clarity.
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Methods: This study aimed to evaluate the optimal approach to assess RV
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function in normotensive patients with acute symptomatic PE. Outcomes assessed through 30-days after the diagnosis of PE included all-cause mortality
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and complicated course.
Results: Eight hundred and forty eight patients were enrolled. Computed tomography (MDCT) and echocardiography (TTE) agreed on the presence or absence of RV overload in 449 (53%) patients. The combination of the simplified Pulmonary Embolism Severity Index (sPESI) and MDCT showed a
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negative predictive value for 30-day all-cause mortality of 100%. Of the 43%
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that had a sPESI of >0 points and MDCT RV enlargement, 41 (11.3%) experienced a complicated course that included 24 (6.6%) deaths. One hundred and twenty nine patients (15%) had a sPESI of >0 points, MDCT and
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echocardiographic RV overload. Of these, 21 (16.3%) experienced a
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complicated course within the first 30 days, and 10 (7.7%) of them died.
Conclusions: Incorporation of echocardiographic RV overload to the sPESI and MDCT did not improve identification of low-risk PE patients, while it improved identification of those at intermediate-high risk for short-term complications.
Abstract word count: 199
Key words: Pulmonary embolism; computed tomography; echocardiography; prognosis.
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INTRODUCTION Pulmonary embolism (PE) is a potentially life-threatening cardiovascular condition (1). Early mortality rates for PE range from less than 5% in clinically
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stable patients to more than 50% in patients that have cardiogenic shock (2-4). Based on risk profiles, some patients with PE (low-risk PE) may safely undergo
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treatment at home and avoid admission to a hospital (5-6), while others may
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require intensive monitoring (intermediate-high risk PE). Risk stratification tools may help with decision-making regarding appropriate management of patients
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with acute PE (7).
A number of echocardiographic parameters permit the non-invasive diagnosis of right ventricular (RV) overload at the bedside. Several registry studies and meta-analyses demonstrated an association between transthoracic echocardiography (TTE)-assessed RV overload in patients with acute PE and
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poor in-hospital outcomes, such as PE-related death and complications (8-10).
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Alternatively, medical centers typically have available and frequently use multidetector (i.e., contrast-enhanced) computed tomography (MDCT) for evaluating and diagnosing patients with suspected PE (11-13). Since MDCT
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allows the visualization and measurement of the heart chambers, it has the potential to provide an alternative to echocardiography for the assessment of
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RV function in patients with acute PE (14-17).
The PROgnosTic valuE of CT scan in hemodynamically stable patients with acute symptomatic pulmonary embolism (PROTECT) study was designed to prospectively assess the prognostic significance of MDCT findings and other cardiovascular prognostic factors in hemodynamically stable patients with acute symptomatic PE (18). The purpose of this study was to evaluate the optimal approach to assess RV function in normotensive patients with acute symptomatic PE.
METHODS Study design
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This substudy used prospectively collected data from patients enrolled in the PROTECT study (18). All patients provided written consent for participation in
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the study in accordance with local ethics committee requirements.
Setting
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Patients underwent recruitment from the Emergency Department (ED) of 5
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academic and 7 general urban hospitals in Spain between January 1, 2009, and
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May 31, 2011.
Study eligibility and patients
The study screened consecutive patients with an objectively confirmed diagnosis of acute symptomatic PE for study participation. Study eligibility required confirmation of the diagnosis of PE with a positive MDCT, and it excluded patients that had hemodynamic instability at presentation (defined as
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cardiogenic shock, systolic blood pressure < 90 mmHg, or use of inotropic
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support), treatment with thrombolytics at the time of PE diagnosis, life expectancy less than 3 months as determined by the investigator, pregnancy, geographic inaccessibility that precluded follow-up, and age younger than 18
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years. The study also required that patients have technically adequate MDCT and TTE studies (18). When pulmonary arterial enhancement was not adequate
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to exclude emboli to the segmental arterial level, radiologists defined MDCT as technically inadequate.
Multidetector computed tomography Each center used standard protocols and multidetector scanners for contrastenhanced evaluation for PE. Trained and certified radiologists at each participating center assessed MDCT RV enlargement by measuring the ratio of the right-to-left ventricular short axis diameters. PROTECT a priori defined MDCT-assessed RV enlargement as a ratio of the RV to the left ventricle (LV) short-axis diameters of greater than 0.9 (19, 20). Methods for establishing interand intra-observer reproducibility for MDCT measurements have been previously published (18).
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Transthoracic echocardiography The study required that patients undergo TTE within 24 hours after diagnosis of PE. Patients underwent testing in the left lateral position. The study defined
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echocardiographic RV overload as the presence of at least two of the following: dilatation of the RV (end-diastolic diameter > 30 mm from the parasternal view
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or the RV appearing larger than the left ventricle from the subcostal or apical
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view), hypokinesis of the RV free wall (any view), and estimated systolic
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pulmonary artery pressure over 30 mm Hg (19, 21).
Calculation of the simplified PESI
Using the baseline data collected at the time of PE diagnosis, the central coordinating center prospectively determined the simplified Pulmonary Embolism Severity Index (sPESI) (22). This score includes the variables of age (> 80 years vs. other), history of cancer (yes/no), history of chronic
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cardiopulmonary disease (yes/no), heart rate (> 110 beats/minute vs. other),
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systolic blood pressure (< 100 mm Hg vs. other), and oxyhemoglobin saturation (< 90% vs. other). The sPESI categorizes patients with none of the variables
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present as low-risk, and those with any variable present as high-risk.
Study endpoints and outcome measures
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PROTECT used all-cause mortality as the primary endpoint. Investigators determined survival status by conducting patient or proxy interviews, and/or hospital chart review. This study used a complicated course after the diagnosis of PE as the secondary endpoint, defined as death from any cause, haemodynamic collapse (systolic blood pressure <90 mm Hg for at least 15 minutes, catecholamine administration because of persistent arterial hypotension or shock, need for thrombolysis, need for endotracheal intubation, or need cardiopulmonary resuscitation), or adjudicated recurrent PE. Study outcomes were assessed for the first 30-days of follow-up after the diagnosis of PE. The Adjudication Committee, whose members were blinded to initial prognostic test results, adjudicated all serious adverse events.
Statistical analyses
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For reporting of continuous data, we used standard descriptive statistics. For non-normally distributed continuous data as determined by KolmogorovSmirnov test, we reported the median and 25th and 75th percentiles. For
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categorical data, we described baseline characteristics with counts and proportions. To assess the test performance characteristics of the sPESI,
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MDCT, and TTE, alone and in combination, we estimated sensitivity, specificity,
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positive and negative predictive values, and positive and negative likelihood ratios. Ninety-five percent confidence intervals (CI) were computed form the
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binomial distribution by using Statistical Package for Social Sciences (SPSS) Statistics 20.0 (IBM, Chicago, IL, USA), and we used Stata, version 11.2 (StataCorp, College Station, Texas) for Windows, for all other analyses.
Source of funding
PROTECT was sponsored by the Institute of Health Carlos III, Spain
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(NCT00880737) (18). The authors are solely responsible for the design and
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RESULTS
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conduct of this study, all study analyses and drafting and editing of the paper.
Study sample
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Between January 1, 2009, and May 31, 2011, the PROTECT study screened 999 normotensive patients with acute PE from 5 academic and 7 general urban hospitals in Spain. The final study cohort consisted of 848 patients (416 men and 432 women) who had a diagnosis of hemodynamically stable acute PE at the time of presentation to the Emergency Department. The patients’ clinical symptoms, predisposing conditions, and relevant findings at presentation are described elsewhere (19). The mean age was 67.4 ± 16.7 years with 49.0% male patients. A history of cardiovascular disease was present in 17.4% of patients, 17.0% had a history of malignancy and 44.2% were diagnosed with concomitant deep vein thrombosis (DVT). The mean sPESI on admission for the PROTECT cohort was 1.1 ± 1.1.
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Of these 848 hemodynamically stable patients with acute symptomatic PE, 535 (63%; 95% CI, 60-66%) patients had a sPESI ≥1 point(s), 533 patients (62.8%; 95% CI 59.6% to 66.1%) had RV enlargement on MDCT, and 192 (22.6%; 95%
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CI 19.8% to 25.5%) had echocardiographic RV overload (Table 1) (Figure 1). MDCT and TTE agreed on the absence of RV overload in 286 (34%) patients,
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and MDCT and TTE agreed on the presence of RV overload in 163 (19%)
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patients (Table 2). Using echocardiography as the reference standard for RV overload, the sensitivity and specificity of MDCT-assessed RV enlargement
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were 85% (95% CI, 79-89%) and 44% (95% CI, 40-48%), with a positive predictive value of 31 (95% CI, 27-35%) and a negative predictive value of 91 (95% CI, 87-94%).
Outcomes
Of the 38 (38/848; 4.5%; 95% CI 3.1% to 5.9%) patients who died during the
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30-day follow-up period, 11 (29.0%) died due to PE. Sixty-three patients (7.4%;
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95% CI, 5.7%-9.2%) had a complicated course. In addition to the 38 deaths (including the two from recurrent PE), complicated course was due to
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hemodynamic collapse in 28 patients and non-fatal symptomatic recurrent PE in
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Identification of low-risk PE Of 315 patients (37% of the entire study population) with negative MDCT for RV enlargement, 20 (6.3%; 95% CI, 3.9-9.6%) experienced a complicated course within the first 30 days, and 13 of them (4.1%; 95% CI, 2.2-6.9%) died (Table 3). Of 313 patients (37% of the entire study population) with a sPESI of 0 points, five (1.6%; 95% CI, 0.5-3.7%) experienced a complicated course within the first 30 days, and only one of them (0.3%; 95% CI, 0-1.8%) died. By combining the prognostic information provided by these two variables, we found that of 143 patients (17% of the entire study population) with a sPESI of 0 points and negative CTPA for RV enlargement, three (2.1%; 95% CI, 0.4-6.0%) experienced a complicated course during the study period, and none of them died (negative predictive value of 100%). In contrast, the addition of TTE did not improve identification of low-risk PE (Table 3).
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Identification of intermediate-high risk PE Of 533 patients (63% of the entire study population) with MDCT-assessed RV
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enlargement, 43 (8.1%; 95% CI, 5.9-10.7%) experienced a complicated course within the first 30 days, and 25 of them (4.7%; 95% CI, 3.1-6.8%) died (Table
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3). Of 535 patients (63% of the entire study population) with a sPESI ≥1
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point(s), 58 (10.8%; 95% CI, 8.3-13.8%) experienced a complicated course within the first 30 days, and 37 of them (6.9%; 95% CI, 4.9-9.4%) died. By combining the prognostic information provided by these two variables, we found
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that of 363 patients (43% of the entire study population) with a sPESI ≥1 point(s) and positive MDCT for RV enlargement, 41 (11.3%; 95% CI, 8.215.0%) experienced a complicated course during the study period, and 24 (6.6%; 95% CI, 4.3-9.7%) died. One hundred and twenty nine (15.2%; 95% CI, 12.9-17.8%) patients with a sPESI ≥1 point(s) and positive MDCT for RV
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enlargement had echocardiographic RV overload, and 21 (16.3%; 95% CI,
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10.4-23.8%) of these patients experienced a complicated course (10 deaths,
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7.7%).
DISCUSSION
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The optimal approach to assess RV function in normotensive patients with acute symptomatic PE lacks clarity. The results of this study suggest that incorporation of RV overload assessed by echocardiography to the sPESI and MDCT did not improve identification of the low-risk PE patients. Alternatively, the combination of a sPESI of >0 points, MDCT- and echocardiographyassessed RV overload improved identification of normotensive patients with acute symptomatic PE at intermediate-high risk for a 30-day complicated course.
Risk stratification should be performed to categorize patients with acute PE according to their risk for short-term complications (23). Evaluation of right heart function has proven to be an integral part of the initial evaluation, with echocardiography being particularly valuable for predicting morbidity and
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mortality. However, TTE requires specialized training for measurement and interpretation. Since information on MDCT-assessed RV enlargement is available for most patients at the time of PE diagnosis, we assessed if the
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prognostic information provided by MDCT might replace RV overload detected using echocardiography for prognosticating patients with acute PE.
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In contrast to a previous study (20), we found that MDCT had a fair accuracy
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when compared with echocardiography for the assessment of RV overload in patients with acute PE. This discrepancy might be attributed to the fact that
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quantification of the RV/left ventricle (LV) ratio by MDCT is subject to a significant inter-reader variability (24). In addition, chest CT image acquisition was not electrocardiogram (ECG) gated in the PROTECT study. Non–ECGgated CT is inevitably inaccurate for measuring ventricular chamber size, because the images are acquired in different phases of the cardiac cycle. However, the use of ECG-gated CT protocols over routine chest CT has been
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shown to result in only limited incremental diagnostic improvements (25).
Clinical prognostic models (i.e., sPESI) help identify low-risk patients with PE who might safely undergo outpatient PE therapy (26, 27). This study further
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supports the applicability of the sPESI as a first step for identifying low-risk patients. Since the combination of sPESI and MDCT allowed for the
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identification of 100% of patients who died during the first thirty days of followup, our results did not support the incorporation of echocardiographic RV overload into the sPESI to identify low-risk normotensive patients with acute PE who might benefit from outpatient therapy. One potential explanation for these results is that short-term prognosis of normotensive patients with acute PE may be more often driven by comorbidities than by PE-related RV overload (28).
Single tests have not demonstrated a sufficient positive predictive value to identify the subgroup of normotensive patients with acute symptomatic PE at increased risk of PE-related complications (i.e., intermediate-high risk subgroup). Multimarker models combining prognostic tools indicating myocardial injury or RV overload have improved the identification of such intermediate-high risk patients. Our results showed that the prognostic accuracy
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of the combination of MDCT-assessed RV enlargement and echocardiographic RV overload had a slight trend toward improvement of the prediction of PErelated complications compared with use of any test by itself. In the setting of
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acute PE, while MDCT only provides indirect signs of RV overload, echocardiography more likely captures the complex hemodynamic changes that
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impact RV function.
Limitations of the study include the retrospective analysis of the cohort,
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although prospectively developed. Despite the large number of patients assessed for this study, the low number of primary endpoints did not allow for more precision in our estimates. One weakness of the study included the restriction of recruitment to patients who could safely undergo the extra tests within 24 hours after diagnosis of PE. It is not apparent whether this affected the results. Though the RV size might be easier to measure on MDCT than
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traditional RV measures on TTE, in the present study the MDCT images were
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done and interpreted by certified radiologists and thus the results cannot be necessarily applied to less experienced operators. Since the aim of this study was to evaluate the optimal approach to assess RV function in normotensive
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patients with acute symptomatic PE, we did not assess whether the combination of cardiac biomarkers and imaging testing will offer additional
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information to clinicians prognosticating patients with acute symptomatic PE.
In conclusion, the results of this study of normotensive patients presenting with acute symptomatic PE suggest that the combination of MDCT negative for RV overload and sPESI = 0 may identify patients at low-risk for death or complicated course over the ensuing 30 days. In addition, the combination of MDCT and echocardiographic assessment of RV function might be required for identifying intermediate-high risk patients with acute symptomatic PE.
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Author contributions Study concept and design: Barrios, Lobo, Yusen, Jiménez Acquisition of data; analysis and interpretation of data; statistical analysis:
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Barrios, Morillo, Lobo, Nieto, Jaureguizar, Portillo, Barbero, Fernández-Golfín, Yusen, Jiménez
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Drafting of the manuscript: Barrios, Morillo, Lobo, Nieto, Jaureguizar, Portillo,
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Study supervision: Barrios, Jiménez
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Barbero, Fernández-Golfín, Yusen, Jiménez
The corresponding author, David Jiménez, had full access to all the data in the
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study and had final responsibility for the decision to submit for publication.
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Conflict of interest statement
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None reported.
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Source of funding: FIS 2008 (PI 08200), SEPAR 2008, NM 2010
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APPENDIX
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Coordinator of the PROTECT Study: David Jiménez
PROTECT Steering Committee Members: David Jiménez, José Luis Lobo,
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Manuel Monreal, Remedios Otero, Roger D. Yusen
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PROTECT Study Coordinating Center: S & H Medical Science Service
Adjudication Committee: Francisco Conget, Dolores Nauffal, Mikel Oribe,
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Fernando Uresandi
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Radiology Panel: Ignacio Gallego, Luis Gorospe, Agustina Vicente
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Blood Sample Processing: José Manuel del Rey
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Statiscian: Víctor Abraira, Javier Zamora, Alfonso Muriel
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Investigators of the PROTECT study Consolación Rodríguez, Jorge Vivancos, Jesús Marín (Bormujos), Mikel Oribe,
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Aitor Ballaz, Jose María Abaitúa, Sonia Velasco (Galdakao), Manuel Barrón, María Lladó, Carmen Rodrigo, Luis Javier Alonso (Logroño), Ramón Rabuñal,
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Olalla Castro, Concepción Iglesias, Ana Testa (Lugo), David Jiménez, Vicente Gómez, Luis Gorospe, Sem Briongos, José Manuel del Rey (Madrid), Celso
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Álvarez, Nuria Rodríguez, Amador Prieto, María Martín (Oviedo), Carmen Navarro, Mónica López, Eva Castañer, Eva Guillaumet (Sabadell), Remedios
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Otero, Teresa Elías, Pilar Serrano, Francisco López (Sevilla), Reina Valle, María Victoria Piret, Pilar Lucio, José María Cuesta (Sierrallana), Dolores Nauffal, Marta Ballester, José Pamies, Ana Osa (Valencia), José Luis Lobo, Vanesa Zorrilla, Delfina Pozo, Ángel Alonso (Vitoria), Francisco Conget, Miguel
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Ángel Santolaria, Mariano González, José Luis de Benito (Zaragoza)
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Figure Legends
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Figure 1. Distribution of patients according to baseline prognostic tests
Figure 2. Frequency of a) 30-day all-cause mortality and b) 30-day
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complicated course according to baseline prognostic tests
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Table 1. Baseline characteristics and treatment information across different high-risk categories
Echocardiographic
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High-risk sPESI
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RV overload N = 192
N = 533
th
76 (65-83)
76 (64-81)
74 (63-81)
percentiles) 184 (34.4%)
56 (29.2%)
138 (25.9%)
Male gender
243 (45.4%)
70 (36.4%)
243 (45.6%)
138 (25.8%)
28 (14.6%)
83 (15.6%)
Recent surgery
39 (7.3%)
10 (5.2%)
51 (9.6%)
Previous VTE
73 (13.6%)
22 (11.5%)
80 (15.0%)
128 (23.9%)
37 (19.3%)
116 (21.8%)
103 (19.3%)
25 (13.0%)
70 (13.1%)
50 (9.3%)
14 (7.3%)
31 (5.8%)
98 (18.3%)
49 (25.5%)
108 (20.3%)
227 (42.4%)
85 (44.3%)
241 (45.2%)
444 (83.0%)
173 (90.1%)
440 (82.5%)
Heart rate > 110/minute
173 (32.3%)
63 (32.8%)
130 (24.4%)
Arterial oxyhemoglobin saturation
185 (34.6%)
77 (40.1%)
136 (25.5%)
34 (6.4%)
9 (4.7%)
24 (4.5%)
BNP > 100 pg/mL
290 (54.2%)
132 (68.8%)
281 (52.7%)
cTnI > 0 ng/mL
111 (20.7%)
65 (33.9%)
116 (21.8%)
8 (1.5%)
0 (0%)
4 (0.7%)
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Age > 80 years
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th
RV enlargement
N = 535 Clinical characteristics, n (%) Age, years, median (25 -75
MDCT-assessed
Cancer† ‡
Immobilization
y
Comorbid diseases, n (%) COPD Congestive heart failure
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Clinical symptoms and signs at presentation, n (%)
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Syncope Chest pain
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Dyspnea
ED
Risk factors for VTE, n (%)
by pulse oximetry < 90% SBP < 100 mm Hg
Cardiac biomarkers, n (%)
Treatment Insertion of an IVC filter
Abbreviations: VTE, venous thromboembolism; COPD, chronic obstructive pulmonary disease; SBP, systolic blood pressure; BNP, brain natriuretic peptide; cTnI, cardiac troponin I; IVC, inferior vena cava; sPESI, simplified Pulmonary Embolism Severity Index; RV, right ventricle; MDCT, multidetector computed tomography. †
Active or under treatment in the last year
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In the previous month
y
Immobilized patients defined as non-surgical patients with limited mobility (i.e., total bed rest with
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bathroom privileges) for ≥4 days in the month prior to PE diagnosis
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Table 2. Patients diagnosed with right ventricular overload on echocardiography and multidetector computed tomography
N = 656 Positive MDCT for RV enlargement N = 315 Negative MDCT for RV enlargement
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N = 533
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286
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overload
Positive TTE for RV
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Negative TTE for RV
overload N = 192 29
163
Abbreviations: TTE, transthoracic echocardiography; RV, right ventricle; MDCT, multidetector computed
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tomography.
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Table 3. Incidence of 30-day complicated course* according to baseline prognostic test results
Negative sPESI
Positive sPESI
N = 848
N = 313
N = 535
Negative MDCT
20/315 (6.3%)
3/143 (2.1%)
17/172 (9.9%)
Positive MDCT
43/533 (8.1%)
2/170 (1.2%)
41/363 (11.3%)
Negative echocardiography
37/656 (5.6%)
3/273 (1.1%)
34/383 (8.9%)
Positive echocardiography
26/192 (13.5%)
2/40 (5.0%)
24/152 (15.8%)
Negative MDCT and negative
17/286 (5.9%)
3/137 (2.2%)
14/149 (9.4%)
Negative MDCT and positive
0/6 (0%)
3/23 (13.0%)
20/370 (5.4%)
0/136 (0%)
20/234 (8.5%)
23/163 (14.1%)
2/34 (5.9%)
21/129 (16.3%)
echocardiography Positive MDCT and positive
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echocardiography
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3/29 (10.3%)
echocardiography Positive MDCT and negative
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echocardiography
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All patients
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Abbreviations: sPESI, simplified Pulmonary Embolism Severity Index; MDCT, multidetector computed tomography.
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*Defined as all-cause mortality, or haemodynamic collapse, or recurrent PE.
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Figure 1 PE, pulmonary embolism
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sPESI, simplified Pulmonary Embolism Severity Index
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MDCT, multidetector computed tomography
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ED
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TTE, transthoracic echocardiography
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Figure 2. Frequency of a) 30-day all-cause mortality and b) 30-day complicated course* according to baseline prognostic tests
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A)
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B)
Abbreviations: sPESI, simplified Pulmonary Embolism Severity Index; MDCT, multidetector computed tomography; RV, right ventricle. *“Complicated course”, defined as death from any cause, haemodynamic collapse (defined as need for cardiopulmonary resuscitation, systolic blood pressure < 90 mm Hg at least for 15 minutes, need for cathecolamine administration, or need for thrombolysis), or adjudicated recurrent PE within the 30-days of follow-up.
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S0002-8703(16)30290-3 doi: 10.1016/j.ahj.2016.12.009 YMHJ 5343
To appear in:
American Heart Journal
Received date: Accepted date:
27 July 2016 22 December 2016
Please cite this article as: Barrios Deisy, Morillo Raquel, Lobo Jos´e Luis, Nieto Rosa, Jaureguizar Ana, Portillo Ana K., Barbero Esther, Fernandez-Golfin Covadonga, Yusen Roger D., Jim´enez David, Assessment of right ventricular function in acute pulmonary embolism, American Heart Journal (2016), doi: 10.1016/j.ahj.2016.12.009
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
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ASSESSMENT OF RIGHT VENTRICULAR FUNCTION IN ACUTE
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PULMONARY EMBOLISM
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Authors:
Deisy Barrios1, Raquel Morillo1, José Luis Lobo2, Rosa Nieto1, Ana
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Jaureguizar1, Ana K. Portillo3, Esther Barbero1, Covadonga Fernandez-Golfin4,
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Roger D. Yusen5, David Jiménez1, the PROTECT investigators
Affiliation: 1
Respiratory Department, Ramón y Cajal Hospital and Universidad de Alcalá IRYCIS,
Madrid, Spain 2
Respiratory Department, Hospital Universitario Araba, Álava, Spain
3
Department of Internal Medicine, Ramón y Cajal Hospital and Instituto Ramón y Cajal
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de Investigación Sanitaria IRYCIS, Madrid, Spain. 4
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Cardiology Department, Ramón y Cajal Hospital and Instituto Ramón y Cajal de
Investigación Sanitaria IRYCIS, Madrid, Spain 5
Divisions of Pulmonary and Critical Care Medicine and General Medical Sciences,
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Washington University School of Medicine, St. Louis, Missouri, USA
Correspondence: David Jiménez
Respiratory Department and Medicine Department Ramón y Cajal Hospital, Universidad de Alcalá IRYCIS 28034 Madrid, Spain Phone: +34913368314 e-mail: [email protected]
Short title: Right ventricle function in PE Word count: 2,376
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HIGHLIGHTS
Multidetector computed tomography (MDCT) and transthoracic echocardiography agree in 53% of patients on the presence or absence of
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right ventricular (RV) overload.
Incorporation of echocardiographic right ventricular overload to the
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simplified PESI and MDCT does not improve identification of low-risk PE
The combination of MDCT and echocardiographic assessment of RV
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function might be required for identifying intermediate-high risk patients with
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PE.
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patients.
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ABSTRACT
Background: The optimal approach to assess right ventricular (RV) function in
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patients with acute symptomatic pulmonary embolism (PE) lacks clarity.
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Methods: This study aimed to evaluate the optimal approach to assess RV
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function in normotensive patients with acute symptomatic PE. Outcomes assessed through 30-days after the diagnosis of PE included all-cause mortality
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and complicated course.
Results: Eight hundred and forty eight patients were enrolled. Computed tomography (MDCT) and echocardiography (TTE) agreed on the presence or absence of RV overload in 449 (53%) patients. The combination of the simplified Pulmonary Embolism Severity Index (sPESI) and MDCT showed a
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negative predictive value for 30-day all-cause mortality of 100%. Of the 43%
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that had a sPESI of >0 points and MDCT RV enlargement, 41 (11.3%) experienced a complicated course that included 24 (6.6%) deaths. One hundred and twenty nine patients (15%) had a sPESI of >0 points, MDCT and
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echocardiographic RV overload. Of these, 21 (16.3%) experienced a
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complicated course within the first 30 days, and 10 (7.7%) of them died.
Conclusions: Incorporation of echocardiographic RV overload to the sPESI and MDCT did not improve identification of low-risk PE patients, while it improved identification of those at intermediate-high risk for short-term complications.
Abstract word count: 199
Key words: Pulmonary embolism; computed tomography; echocardiography; prognosis.
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INTRODUCTION Pulmonary embolism (PE) is a potentially life-threatening cardiovascular condition (1). Early mortality rates for PE range from less than 5% in clinically
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stable patients to more than 50% in patients that have cardiogenic shock (2-4). Based on risk profiles, some patients with PE (low-risk PE) may safely undergo
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treatment at home and avoid admission to a hospital (5-6), while others may
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require intensive monitoring (intermediate-high risk PE). Risk stratification tools may help with decision-making regarding appropriate management of patients
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with acute PE (7).
A number of echocardiographic parameters permit the non-invasive diagnosis of right ventricular (RV) overload at the bedside. Several registry studies and meta-analyses demonstrated an association between transthoracic echocardiography (TTE)-assessed RV overload in patients with acute PE and
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poor in-hospital outcomes, such as PE-related death and complications (8-10).
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Alternatively, medical centers typically have available and frequently use multidetector (i.e., contrast-enhanced) computed tomography (MDCT) for evaluating and diagnosing patients with suspected PE (11-13). Since MDCT
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allows the visualization and measurement of the heart chambers, it has the potential to provide an alternative to echocardiography for the assessment of
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RV function in patients with acute PE (14-17).
The PROgnosTic valuE of CT scan in hemodynamically stable patients with acute symptomatic pulmonary embolism (PROTECT) study was designed to prospectively assess the prognostic significance of MDCT findings and other cardiovascular prognostic factors in hemodynamically stable patients with acute symptomatic PE (18). The purpose of this study was to evaluate the optimal approach to assess RV function in normotensive patients with acute symptomatic PE.
METHODS Study design
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This substudy used prospectively collected data from patients enrolled in the PROTECT study (18). All patients provided written consent for participation in
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the study in accordance with local ethics committee requirements.
Setting
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Patients underwent recruitment from the Emergency Department (ED) of 5
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academic and 7 general urban hospitals in Spain between January 1, 2009, and
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May 31, 2011.
Study eligibility and patients
The study screened consecutive patients with an objectively confirmed diagnosis of acute symptomatic PE for study participation. Study eligibility required confirmation of the diagnosis of PE with a positive MDCT, and it excluded patients that had hemodynamic instability at presentation (defined as
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cardiogenic shock, systolic blood pressure < 90 mmHg, or use of inotropic
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support), treatment with thrombolytics at the time of PE diagnosis, life expectancy less than 3 months as determined by the investigator, pregnancy, geographic inaccessibility that precluded follow-up, and age younger than 18
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years. The study also required that patients have technically adequate MDCT and TTE studies (18). When pulmonary arterial enhancement was not adequate
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to exclude emboli to the segmental arterial level, radiologists defined MDCT as technically inadequate.
Multidetector computed tomography Each center used standard protocols and multidetector scanners for contrastenhanced evaluation for PE. Trained and certified radiologists at each participating center assessed MDCT RV enlargement by measuring the ratio of the right-to-left ventricular short axis diameters. PROTECT a priori defined MDCT-assessed RV enlargement as a ratio of the RV to the left ventricle (LV) short-axis diameters of greater than 0.9 (19, 20). Methods for establishing interand intra-observer reproducibility for MDCT measurements have been previously published (18).
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Transthoracic echocardiography The study required that patients undergo TTE within 24 hours after diagnosis of PE. Patients underwent testing in the left lateral position. The study defined
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echocardiographic RV overload as the presence of at least two of the following: dilatation of the RV (end-diastolic diameter > 30 mm from the parasternal view
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or the RV appearing larger than the left ventricle from the subcostal or apical
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view), hypokinesis of the RV free wall (any view), and estimated systolic
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pulmonary artery pressure over 30 mm Hg (19, 21).
Calculation of the simplified PESI
Using the baseline data collected at the time of PE diagnosis, the central coordinating center prospectively determined the simplified Pulmonary Embolism Severity Index (sPESI) (22). This score includes the variables of age (> 80 years vs. other), history of cancer (yes/no), history of chronic
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cardiopulmonary disease (yes/no), heart rate (> 110 beats/minute vs. other),
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systolic blood pressure (< 100 mm Hg vs. other), and oxyhemoglobin saturation (< 90% vs. other). The sPESI categorizes patients with none of the variables
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present as low-risk, and those with any variable present as high-risk.
Study endpoints and outcome measures
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PROTECT used all-cause mortality as the primary endpoint. Investigators determined survival status by conducting patient or proxy interviews, and/or hospital chart review. This study used a complicated course after the diagnosis of PE as the secondary endpoint, defined as death from any cause, haemodynamic collapse (systolic blood pressure <90 mm Hg for at least 15 minutes, catecholamine administration because of persistent arterial hypotension or shock, need for thrombolysis, need for endotracheal intubation, or need cardiopulmonary resuscitation), or adjudicated recurrent PE. Study outcomes were assessed for the first 30-days of follow-up after the diagnosis of PE. The Adjudication Committee, whose members were blinded to initial prognostic test results, adjudicated all serious adverse events.
Statistical analyses
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For reporting of continuous data, we used standard descriptive statistics. For non-normally distributed continuous data as determined by KolmogorovSmirnov test, we reported the median and 25th and 75th percentiles. For
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categorical data, we described baseline characteristics with counts and proportions. To assess the test performance characteristics of the sPESI,
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MDCT, and TTE, alone and in combination, we estimated sensitivity, specificity,
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positive and negative predictive values, and positive and negative likelihood ratios. Ninety-five percent confidence intervals (CI) were computed form the
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binomial distribution by using Statistical Package for Social Sciences (SPSS) Statistics 20.0 (IBM, Chicago, IL, USA), and we used Stata, version 11.2 (StataCorp, College Station, Texas) for Windows, for all other analyses.
Source of funding
PROTECT was sponsored by the Institute of Health Carlos III, Spain
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(NCT00880737) (18). The authors are solely responsible for the design and
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RESULTS
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conduct of this study, all study analyses and drafting and editing of the paper.
Study sample
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Between January 1, 2009, and May 31, 2011, the PROTECT study screened 999 normotensive patients with acute PE from 5 academic and 7 general urban hospitals in Spain. The final study cohort consisted of 848 patients (416 men and 432 women) who had a diagnosis of hemodynamically stable acute PE at the time of presentation to the Emergency Department. The patients’ clinical symptoms, predisposing conditions, and relevant findings at presentation are described elsewhere (19). The mean age was 67.4 ± 16.7 years with 49.0% male patients. A history of cardiovascular disease was present in 17.4% of patients, 17.0% had a history of malignancy and 44.2% were diagnosed with concomitant deep vein thrombosis (DVT). The mean sPESI on admission for the PROTECT cohort was 1.1 ± 1.1.
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Of these 848 hemodynamically stable patients with acute symptomatic PE, 535 (63%; 95% CI, 60-66%) patients had a sPESI ≥1 point(s), 533 patients (62.8%; 95% CI 59.6% to 66.1%) had RV enlargement on MDCT, and 192 (22.6%; 95%
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CI 19.8% to 25.5%) had echocardiographic RV overload (Table 1) (Figure 1). MDCT and TTE agreed on the absence of RV overload in 286 (34%) patients,
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and MDCT and TTE agreed on the presence of RV overload in 163 (19%)
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patients (Table 2). Using echocardiography as the reference standard for RV overload, the sensitivity and specificity of MDCT-assessed RV enlargement
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were 85% (95% CI, 79-89%) and 44% (95% CI, 40-48%), with a positive predictive value of 31 (95% CI, 27-35%) and a negative predictive value of 91 (95% CI, 87-94%).
Outcomes
Of the 38 (38/848; 4.5%; 95% CI 3.1% to 5.9%) patients who died during the
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30-day follow-up period, 11 (29.0%) died due to PE. Sixty-three patients (7.4%;
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95% CI, 5.7%-9.2%) had a complicated course. In addition to the 38 deaths (including the two from recurrent PE), complicated course was due to
1 patient.
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hemodynamic collapse in 28 patients and non-fatal symptomatic recurrent PE in
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Identification of low-risk PE Of 315 patients (37% of the entire study population) with negative MDCT for RV enlargement, 20 (6.3%; 95% CI, 3.9-9.6%) experienced a complicated course within the first 30 days, and 13 of them (4.1%; 95% CI, 2.2-6.9%) died (Table 3). Of 313 patients (37% of the entire study population) with a sPESI of 0 points, five (1.6%; 95% CI, 0.5-3.7%) experienced a complicated course within the first 30 days, and only one of them (0.3%; 95% CI, 0-1.8%) died. By combining the prognostic information provided by these two variables, we found that of 143 patients (17% of the entire study population) with a sPESI of 0 points and negative CTPA for RV enlargement, three (2.1%; 95% CI, 0.4-6.0%) experienced a complicated course during the study period, and none of them died (negative predictive value of 100%). In contrast, the addition of TTE did not improve identification of low-risk PE (Table 3).
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Identification of intermediate-high risk PE Of 533 patients (63% of the entire study population) with MDCT-assessed RV
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enlargement, 43 (8.1%; 95% CI, 5.9-10.7%) experienced a complicated course within the first 30 days, and 25 of them (4.7%; 95% CI, 3.1-6.8%) died (Table
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3). Of 535 patients (63% of the entire study population) with a sPESI ≥1
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point(s), 58 (10.8%; 95% CI, 8.3-13.8%) experienced a complicated course within the first 30 days, and 37 of them (6.9%; 95% CI, 4.9-9.4%) died. By combining the prognostic information provided by these two variables, we found
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that of 363 patients (43% of the entire study population) with a sPESI ≥1 point(s) and positive MDCT for RV enlargement, 41 (11.3%; 95% CI, 8.215.0%) experienced a complicated course during the study period, and 24 (6.6%; 95% CI, 4.3-9.7%) died. One hundred and twenty nine (15.2%; 95% CI, 12.9-17.8%) patients with a sPESI ≥1 point(s) and positive MDCT for RV
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enlargement had echocardiographic RV overload, and 21 (16.3%; 95% CI,
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10.4-23.8%) of these patients experienced a complicated course (10 deaths,
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7.7%).
DISCUSSION
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The optimal approach to assess RV function in normotensive patients with acute symptomatic PE lacks clarity. The results of this study suggest that incorporation of RV overload assessed by echocardiography to the sPESI and MDCT did not improve identification of the low-risk PE patients. Alternatively, the combination of a sPESI of >0 points, MDCT- and echocardiographyassessed RV overload improved identification of normotensive patients with acute symptomatic PE at intermediate-high risk for a 30-day complicated course.
Risk stratification should be performed to categorize patients with acute PE according to their risk for short-term complications (23). Evaluation of right heart function has proven to be an integral part of the initial evaluation, with echocardiography being particularly valuable for predicting morbidity and
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mortality. However, TTE requires specialized training for measurement and interpretation. Since information on MDCT-assessed RV enlargement is available for most patients at the time of PE diagnosis, we assessed if the
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prognostic information provided by MDCT might replace RV overload detected using echocardiography for prognosticating patients with acute PE.
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In contrast to a previous study (20), we found that MDCT had a fair accuracy
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when compared with echocardiography for the assessment of RV overload in patients with acute PE. This discrepancy might be attributed to the fact that
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quantification of the RV/left ventricle (LV) ratio by MDCT is subject to a significant inter-reader variability (24). In addition, chest CT image acquisition was not electrocardiogram (ECG) gated in the PROTECT study. Non–ECGgated CT is inevitably inaccurate for measuring ventricular chamber size, because the images are acquired in different phases of the cardiac cycle. However, the use of ECG-gated CT protocols over routine chest CT has been
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shown to result in only limited incremental diagnostic improvements (25).
Clinical prognostic models (i.e., sPESI) help identify low-risk patients with PE who might safely undergo outpatient PE therapy (26, 27). This study further
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supports the applicability of the sPESI as a first step for identifying low-risk patients. Since the combination of sPESI and MDCT allowed for the
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identification of 100% of patients who died during the first thirty days of followup, our results did not support the incorporation of echocardiographic RV overload into the sPESI to identify low-risk normotensive patients with acute PE who might benefit from outpatient therapy. One potential explanation for these results is that short-term prognosis of normotensive patients with acute PE may be more often driven by comorbidities than by PE-related RV overload (28).
Single tests have not demonstrated a sufficient positive predictive value to identify the subgroup of normotensive patients with acute symptomatic PE at increased risk of PE-related complications (i.e., intermediate-high risk subgroup). Multimarker models combining prognostic tools indicating myocardial injury or RV overload have improved the identification of such intermediate-high risk patients. Our results showed that the prognostic accuracy
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of the combination of MDCT-assessed RV enlargement and echocardiographic RV overload had a slight trend toward improvement of the prediction of PErelated complications compared with use of any test by itself. In the setting of
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acute PE, while MDCT only provides indirect signs of RV overload, echocardiography more likely captures the complex hemodynamic changes that
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impact RV function.
Limitations of the study include the retrospective analysis of the cohort,
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although prospectively developed. Despite the large number of patients assessed for this study, the low number of primary endpoints did not allow for more precision in our estimates. One weakness of the study included the restriction of recruitment to patients who could safely undergo the extra tests within 24 hours after diagnosis of PE. It is not apparent whether this affected the results. Though the RV size might be easier to measure on MDCT than
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traditional RV measures on TTE, in the present study the MDCT images were
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done and interpreted by certified radiologists and thus the results cannot be necessarily applied to less experienced operators. Since the aim of this study was to evaluate the optimal approach to assess RV function in normotensive
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patients with acute symptomatic PE, we did not assess whether the combination of cardiac biomarkers and imaging testing will offer additional
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information to clinicians prognosticating patients with acute symptomatic PE.
In conclusion, the results of this study of normotensive patients presenting with acute symptomatic PE suggest that the combination of MDCT negative for RV overload and sPESI = 0 may identify patients at low-risk for death or complicated course over the ensuing 30 days. In addition, the combination of MDCT and echocardiographic assessment of RV function might be required for identifying intermediate-high risk patients with acute symptomatic PE.
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24. Kang DK, Thilo C, Schoepf UJ, Barraza JM Jr, Nance JW Jr, Bastarrika G, Abro JA, Ravenel JG, Costello P, Goldhaber SZ. CT signs of right ventricular dysfunction: prognostic role in acute pulmonary embolism. JACC
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Author contributions Study concept and design: Barrios, Lobo, Yusen, Jiménez Acquisition of data; analysis and interpretation of data; statistical analysis:
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Barrios, Morillo, Lobo, Nieto, Jaureguizar, Portillo, Barbero, Fernández-Golfín, Yusen, Jiménez
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Drafting of the manuscript: Barrios, Morillo, Lobo, Nieto, Jaureguizar, Portillo,
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Study supervision: Barrios, Jiménez
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Barbero, Fernández-Golfín, Yusen, Jiménez
The corresponding author, David Jiménez, had full access to all the data in the
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study and had final responsibility for the decision to submit for publication.
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Conflict of interest statement
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None reported.
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Source of funding: FIS 2008 (PI 08200), SEPAR 2008, NM 2010
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APPENDIX
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Coordinator of the PROTECT Study: David Jiménez
PROTECT Steering Committee Members: David Jiménez, José Luis Lobo,
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Manuel Monreal, Remedios Otero, Roger D. Yusen
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PROTECT Study Coordinating Center: S & H Medical Science Service
Adjudication Committee: Francisco Conget, Dolores Nauffal, Mikel Oribe,
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Fernando Uresandi
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Radiology Panel: Ignacio Gallego, Luis Gorospe, Agustina Vicente
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Blood Sample Processing: José Manuel del Rey
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Statiscian: Víctor Abraira, Javier Zamora, Alfonso Muriel
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Investigators of the PROTECT study Consolación Rodríguez, Jorge Vivancos, Jesús Marín (Bormujos), Mikel Oribe,
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Aitor Ballaz, Jose María Abaitúa, Sonia Velasco (Galdakao), Manuel Barrón, María Lladó, Carmen Rodrigo, Luis Javier Alonso (Logroño), Ramón Rabuñal,
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Olalla Castro, Concepción Iglesias, Ana Testa (Lugo), David Jiménez, Vicente Gómez, Luis Gorospe, Sem Briongos, José Manuel del Rey (Madrid), Celso
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Álvarez, Nuria Rodríguez, Amador Prieto, María Martín (Oviedo), Carmen Navarro, Mónica López, Eva Castañer, Eva Guillaumet (Sabadell), Remedios
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Otero, Teresa Elías, Pilar Serrano, Francisco López (Sevilla), Reina Valle, María Victoria Piret, Pilar Lucio, José María Cuesta (Sierrallana), Dolores Nauffal, Marta Ballester, José Pamies, Ana Osa (Valencia), José Luis Lobo, Vanesa Zorrilla, Delfina Pozo, Ángel Alonso (Vitoria), Francisco Conget, Miguel
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Ángel Santolaria, Mariano González, José Luis de Benito (Zaragoza)
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Figure Legends
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Figure 1. Distribution of patients according to baseline prognostic tests
Figure 2. Frequency of a) 30-day all-cause mortality and b) 30-day
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complicated course according to baseline prognostic tests
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Table 1. Baseline characteristics and treatment information across different high-risk categories
Echocardiographic
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High-risk sPESI
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RV overload N = 192
N = 533
th
76 (65-83)
76 (64-81)
74 (63-81)
percentiles) 184 (34.4%)
56 (29.2%)
138 (25.9%)
Male gender
243 (45.4%)
70 (36.4%)
243 (45.6%)
138 (25.8%)
28 (14.6%)
83 (15.6%)
Recent surgery
39 (7.3%)
10 (5.2%)
51 (9.6%)
Previous VTE
73 (13.6%)
22 (11.5%)
80 (15.0%)
128 (23.9%)
37 (19.3%)
116 (21.8%)
103 (19.3%)
25 (13.0%)
70 (13.1%)
50 (9.3%)
14 (7.3%)
31 (5.8%)
98 (18.3%)
49 (25.5%)
108 (20.3%)
227 (42.4%)
85 (44.3%)
241 (45.2%)
444 (83.0%)
173 (90.1%)
440 (82.5%)
Heart rate > 110/minute
173 (32.3%)
63 (32.8%)
130 (24.4%)
Arterial oxyhemoglobin saturation
185 (34.6%)
77 (40.1%)
136 (25.5%)
34 (6.4%)
9 (4.7%)
24 (4.5%)
BNP > 100 pg/mL
290 (54.2%)
132 (68.8%)
281 (52.7%)
cTnI > 0 ng/mL
111 (20.7%)
65 (33.9%)
116 (21.8%)
8 (1.5%)
0 (0%)
4 (0.7%)
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Age > 80 years
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RV enlargement
N = 535 Clinical characteristics, n (%) Age, years, median (25 -75
MDCT-assessed
Cancer† ‡
Immobilization
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Comorbid diseases, n (%) COPD Congestive heart failure
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Clinical symptoms and signs at presentation, n (%)
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Syncope Chest pain
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Dyspnea
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Risk factors for VTE, n (%)
by pulse oximetry < 90% SBP < 100 mm Hg
Cardiac biomarkers, n (%)
Treatment Insertion of an IVC filter
Abbreviations: VTE, venous thromboembolism; COPD, chronic obstructive pulmonary disease; SBP, systolic blood pressure; BNP, brain natriuretic peptide; cTnI, cardiac troponin I; IVC, inferior vena cava; sPESI, simplified Pulmonary Embolism Severity Index; RV, right ventricle; MDCT, multidetector computed tomography. †
Active or under treatment in the last year
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In the previous month
y
Immobilized patients defined as non-surgical patients with limited mobility (i.e., total bed rest with
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bathroom privileges) for ≥4 days in the month prior to PE diagnosis
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Table 2. Patients diagnosed with right ventricular overload on echocardiography and multidetector computed tomography
N = 656 Positive MDCT for RV enlargement N = 315 Negative MDCT for RV enlargement
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N = 533
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286
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overload
Positive TTE for RV
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Negative TTE for RV
overload N = 192 29
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Abbreviations: TTE, transthoracic echocardiography; RV, right ventricle; MDCT, multidetector computed
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tomography.
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Table 3. Incidence of 30-day complicated course* according to baseline prognostic test results
Negative sPESI
Positive sPESI
N = 848
N = 313
N = 535
Negative MDCT
20/315 (6.3%)
3/143 (2.1%)
17/172 (9.9%)
Positive MDCT
43/533 (8.1%)
2/170 (1.2%)
41/363 (11.3%)
Negative echocardiography
37/656 (5.6%)
3/273 (1.1%)
34/383 (8.9%)
Positive echocardiography
26/192 (13.5%)
2/40 (5.0%)
24/152 (15.8%)
Negative MDCT and negative
17/286 (5.9%)
3/137 (2.2%)
14/149 (9.4%)
Negative MDCT and positive
0/6 (0%)
3/23 (13.0%)
20/370 (5.4%)
0/136 (0%)
20/234 (8.5%)
23/163 (14.1%)
2/34 (5.9%)
21/129 (16.3%)
echocardiography Positive MDCT and positive
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echocardiography
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3/29 (10.3%)
echocardiography Positive MDCT and negative
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All patients
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Abbreviations: sPESI, simplified Pulmonary Embolism Severity Index; MDCT, multidetector computed tomography.
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*Defined as all-cause mortality, or haemodynamic collapse, or recurrent PE.
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Figure 1 PE, pulmonary embolism
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sPESI, simplified Pulmonary Embolism Severity Index
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MDCT, multidetector computed tomography
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TTE, transthoracic echocardiography
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Figure 2. Frequency of a) 30-day all-cause mortality and b) 30-day complicated course* according to baseline prognostic tests
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A)
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Abbreviations: sPESI, simplified Pulmonary Embolism Severity Index; MDCT, multidetector computed tomography; RV, right ventricle. *“Complicated course”, defined as death from any cause, haemodynamic collapse (defined as need for cardiopulmonary resuscitation, systolic blood pressure < 90 mm Hg at least for 15 minutes, need for cathecolamine administration, or need for thrombolysis), or adjudicated recurrent PE within the 30-days of follow-up.
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