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Multidetector CT Scan for Acute Pulmonary Embolism
CHEST
Original Research PULMONARY VASCULAR DISEASE
Multidetector CT Scan for Acute Pulmonary Embolism Embolic Burden and Clinical Outcome Maria Cristina Vedovati, MD; Cecilia Becattini, MD; Giancarlo Agnelli, MD; Pieter W. Kamphuisen, MD; Luca Masotti, MD; Piotr Pruszczyk, MD; Franco Casazza, MD; Aldo Salvi, MD; Stefano Grifoni, MD; Anna Carugati, MD; Stavros Konstantinides, MD; Marthe Schreuder, MD; Marek Golebiowski, MD; and Michele Duranti, MD
Background: In patients with acute pulmonary embolism (PE), the correlation between the embolic burden assessed by multidetector CT (MDCT) scan and clinical outcomes remains unclear. Patients with symptomatic acute PE diagnosed based on MDCT angiography were included in a multicenter study aimed at assessing the prognostic role of the embolic burden evaluated with MDCT scan. Methods: Embolic burden was assessed as (1) localization of the emboli as central (saddle or at least one main pulmonary artery), lobar, or distal (segmental or subsegmental arteries) and (2) the obstruction index by the scoring system of Qanadli. The primary outcome was 30-day all-cause death or clinical deterioration. Predictors of all-cause death or clinical deterioration were identified by Cox regression statistics. Results: Overall, 579 patients were included in the study; 60 (10.4%) died or had clinical deterioration at 30 days. Central localization of emboli was not associated with all-cause death or clinical deterioration (hazard ratio [HR], 2.42; 95% CI, 0.77-7.59; P 5 .13). However, in 516 hemodynamically stable patients, central localization of emboli (HR, 8.3; 95% CI, 1.0-67; P 5 .047) was an independent predictor of all-cause death or clinical deterioration, whereas distal emboli were inversely associated with these outcome events (HR, 0.12; 95% CI, 0.015-0.97; P 5 .047). No correlation was found between obstruction index (evaluated in 448 patients) and all-cause death or clinical deterioration in the overall study population and in the hemodynamically stable patients. Conclusions: In hemodynamically stable patients with acute PE, central emboli are associated with an increased risk for all-cause death or clinical deterioration. This risk is low in patients with segmental or subsegmental PE. CHEST 2012; 142(6):1417–1424 Abbreviations: HR 5 hazard ratio; MDCT 5 multidetector CT; OI 5 obstruction index; PE 5 pulmonary embolism; RVD 5 right ventricle dysfunction
pulmonary embolism (PE) is a potentially Acute fatal disease with a wide spectrum of clinical pre-
sentations. Risk stratification is recommended for driving the clinical management of patients with acute PE.1,2 In hemodynamically stable patients, risk stratification is mainly based on the evaluation of markers of myocardial injury (elevated serum troponin level) and myocardial dysfunction (right ventricle dysfunction [RVD]). The presence of RVD on echocardiography is associated with an increased risk for in-hospital mortality (risk ratio, 2.5; 95% CI, 1.2-5.5).3
Multidetector CT (MDCT) angiography is the most commonly used procedure for the diagnosis of PE. By visualizing the heart chambers and allowing the assessment of RVD, MDCT scan has the potential to contribute to prognostic stratification of patients with PE.4,5 In the most recent guidelines of the European Society of Cardiology and of the American Heart Association, hemodynamic status and markers of myocardial dysfunction or injury replaced the burden of emboli on pulmonary angiography for the stratification
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of severity of PE.2,6 Studies evaluated the prognostic value of the burden of emboli as assessed by MDCT scan in patients with acute PE.7-11 The burden of emboli has been assessed by MDCT angiography as the localization of emboli in different branches of the pulmonary artery10-12 or as a global estimate of the degree of obstruction (obstruction index [OI]).7-9 However, the correlation between the localization of the emboli or the OI assessed by MDCT angiography and the clinical outcome remains unclear. We performed a multicenter study aimed at assessing the prognostic role of the localization of the emboli and of the OI evaluated by MDCT scan in patients with acute PE.
The primary study outcome was 30-day all-cause death or clinical deterioration both in the overall population and in hemodynamically stable patients with PE. Clinical deterioration was defined as the occurrence of one or more of the following events: shock (systemic systolic BP , 90 mm Hg or a drop by ⱖ 40 mm Hg for . 15 min with signs of peripheral hypoperfusion), need for rescue thrombolysis, endotracheal intubation, cathecholamine infusion, or CPR.13 Hemodynamic stability was defined as a value of systemic systolic BP . 90 mm Hg with no signs of peripheral hypoperfusion. In case of death, the presumed cause was reported. PE was considered the cause of death if it was confirmed on autopsy and in case of sudden death that could not be explained by a more compelling alternative diagnosis. The study was approved by local institutional review boards (Comitato Etico delle Aziende Sanitarie Umbre: 984/06). All patients gave written informed consent for inclusion in the study and for the data analysis. Data Collection
Materials and Methods Patients Patients with symptomatic acute PE by MDCT angiography were included in the study provided that data on 30-day follow-up were available. Patients with inadequate MDCT scans (poor imaging) were excluded. Any decision about treatment was at the discretion of the attending physician. Study Design This international, multicenter, prospective cohort study in patients with acute PE was performed in nine centers in Italy, Poland, Germany, and The Netherlands between October 2008 and May 2010. Inpatients from cardiology, emergency, or internal medicine departments were included. The study was aimed at assessing the prognostic value of (1) the localization of the emboli and (2) the burden of emboli (measured as OI) as detected by MDCT angiography. Manuscript received November 4, 2011; revision accepted April 1, 2012. Affiliations: From the Internal and Cardiovascular Medicine– Stroke Unit (Drs Vedovati, Becattini, and Agnelli), University of Perugia, and Department of Radiology (Dr Duranti), S Maria della Misericordia Hospital, Perugia, Italy; Department of Vascular Medicine (Drs Kamphuisen and Schreuder), University Medical Center Groningen, Groningen, The Netherlands; Department of Internal Medicine (Dr Masotti), Cecina Hospital, Cecina, Italy; Department of Internal Medicine and Cardiology (Dr Pruszczyk) and Department of Radiology (Dr Golebiowski), Warsaw Medical University, Warsaw, Poland; Department of Cardiology (Dr Casazza), San Carlo Borromeo Hospital, Milan, Italy; Department of Emergency Medicine (Dr Salvi), Ancona Hospital, Ancona, Italy; Department of Emergency Medicine (Dr Grifoni), Careggi Hospital, Florence, Italy; Department of Internal Medicine (Dr Carugati), Valduce Hospital, Como, Italy; and Department of Cardiology (Dr Konstantinides), Democritus University of Thrace, Alexandroupolis, Greece. Funding/Support: The authors have reported to CHEST that no funding was received for this study. Correspondence to: Maria Cristina Vedovati, MD, Internal and Cardiovascular Medicine–Stroke Unit, via G. Dottori, S. Maria della Misericordia Hospital, 06123 Perugia, Italy; e-mail: [email protected] © 2012 American College of Chest Physicians. Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details. DOI: 10.1378/chest.11-2739
For all patients, the following data were collected: demographic features (age, sex), clinical presentation (signs, symptoms, hemodynamic status, etc), medical history (cancer, COPD, congestive heart failure, etc), laboratory (serum troponin levels) and echocardiographic findings (RVD), anticoagulant treatment, and clinical outcome. Serum troponin level was considered elevated or normal based on local assays and cutoff values. The diagnosis of RVD required the presence of at least two of the following: right-to-left ventricular end-diastolic diameter ratio . 0.9 in the apical four-chamber view, right-to-left ventricular end-diastolic diameter ratio . 0.7 in the parasternal long-axis or subcostal fourchamber views, paradoxical interventricular septal motion, or systolic pulmonary artery pressure . 30 mm Hg.2-4,14 MDCT Angiography Standard contrast-enhanced protocols for the diagnosis of PE were used. See e-Appendix 1 for a list of the CT scanners used at each study location. Standardized dose rate and total dose of contrast medium were used. Image acquisition was started with a scanning delay of 15 to 20 s after the start of the IV injection of contrast medium. MDCT scans were recorded on CDs and centrally assessed for both localization and burden of emboli. The localization of the emboli was evaluated and categorized as follows: central (saddle or at least one main pulmonary artery), lobar (at least one lobar artery), distal (segmental or subsegmental pulmonary arteries), monolateral, or bilateral. The OI was calculated according to the scoring system of Qanadli.7 The score was calculated as N 3 D, where N is the value of the proximal clot site equal to the number of segmental branches arising distally, and D is the degree of obstruction score distinguished as partial (value 5 1) or total (value 5 2). The maximum score is 40 (thrombus completely obstructing the main pulmonary artery), which corresponds to an OI of 100%. Localization of the emboli and OI were centrally determined by a panel comprising a radiologist (M. D.) and at least two of three internal medicine physicians (M. C. V., C. B., and M. S.), who were unaware of the clinical status and outcome. Statistical Analysis Data are reported as proportions or as mean ⫾ SD. Student t test was used for comparisons of continuous data between groups, and x2 test was used for comparisons of dichotomous variables. P , .05 indicates statistical significance in all the analyses. All P values are two sided. Cox regression analysis was used to assess predictors of all-cause death or clinical deterioration. Results are reported as hazard ratios (HRs) and 95% CIs. The following variables were considered in the multivariable analysis:
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Original Research
demographic features (age, sex), comorbidity (cancer), laboratory findings (serum troponin level), RVD on echocardiography, and CT scan findings. Assumption of proportional hazard was assessed and satisfied by visual inspection of the log-minus-log survival curves for localization of emboli. Interobserver agreement was tested by the intraclass correlation coefficient or the k coefficient. All analyses were performed using SPSS, version 11.0 (IBM) statistical software.
Results Overall, 614 patients with acute symptomatic MDCT scan-confirmed PE were evaluated, and 579 patients were included in the study. The flow diagram for inclusion in the study is shown in Figure 1. Five hundred sixteen patients (89%) were hemodynamically stable at admission. Mean age was 69 ⫾ 16 years (range, 18-98 years), and 47.7% were men. Patient characteristics are shown in Table 1. During the 30-day follow-up period, 60 patients (10.4%) died or had clinical deterioration. Thirty-four patients (5.9%) died, of whom 17 (2.9%) died presumably of PE. Localization of the Emboli Localization of emboli was central in 348 patients (60%), lobar in 144 (25%), and distal in 87 (15%). Saddle emboli were observed in 78 (13.5%) and subsegmental emboli in 27 (4.8%). PE was bilateral in 446 (77%). The k index for interobserver agreement was 0.82. No correlation was found between the localization of emboli and age or sex. Dyspnea, concomitant DVT, and obesity were significantly more common in patients with than in patients without a central localization of the emboli (Table 2). Distal emboli were inversely associated with dyspnea, tachycardia, or concomitant DVT. Bilateral PE was associated with dyspnea, tachycardia, and obesity. Elevated levels of serum troponin and the presence of RVD at echocardiography were more common in patients with central or bilateral emboli (Table 2). An inverse association was found
Figure 1. Flow diagram for inclusion in the study. MDCT 5 multidetector CT; OI 5 obstruction index.
Table 1—Characteristics of the Study Population Characteristic
Value
Male sex Age, y Risk factors Concomitant DVT Obesity Cancer Immobilization Trauma Recent surgery COPD Symptoms at presentation Dyspnea Chest pain Hemoptysis Tachycardia Elevated serum troponin level RVD at echocardiography Thrombolytic treatment
276 (47.7) 68.5 ⫾ 16.3 417 (72.0) 48 (8.3) 123 (21.2) 71 (12.3) 44 (7.6) 28 (4.8) 60 (10.4) 473 (81.7) 212 (36.6) 16 (2.8) 243 (42.0) 261 (45.0) 302 (52.2) 41(7.1)
Data are presented as No. (%) or mean ⫾ SD. RVD 5 right ventricle dysfunction.
between distal emboli and elevated levels of serum troponin or RVD on echocardiography. The incidence of all-cause death or clinical deterioration was 11.2%, 11.1%, and 5.7% in patients with central, lobar, and distal emboli, respectively. At multivariate analysis, no association was found between localization of emboli and all-cause death or clinical deterioration in the overall population (central emboli HR, 2.42; 95% CI, 0.77-7.59; lobar emboli HR, 2.15; 95% CI, 0.70-6.55; distal emboli HR, 0.41; 95% CI, 0.13-1.30; all P not significant) (Fig 2). Age . 75 years (HR, 1.72; 95% CI, 1.01-2.94; P 5 .046), RVD on echocardiography (HR, 2.57; 95% CI, 1.36-4.89; P 5 .004), and hypotension at presentation (HR, 5.08; 95% CI, 2.97-8.69; P , .001) were independent predictors of adverse outcome. When the analysis was restricted to the 516 initially hemodynamically stable patients, the rate of all-cause death or clinical deterioration was 8.4%, 7.8%, and 2.6% in patients with central, lobar, and distal emboli, respectively. In these patients, central emboli (HR, 8.3; 95% CI, 1.0-67; P 5 .047), age . 75 years (HR, 2.6; 95% CI, 1.3-5.2; P 5 .008), and RVD on echocardiography (HR, 2.4; 95% CI, 1.1-5.2; P 5 .029) were independent predictors of all-cause death or clinical deterioration (Fig 3). Distal localization of emboli was associated with a reduced risk for these outcome events (HR, 0.12; 95% CI, 0.01-0.97; P 5 .047). Patients with lobar emboli had a higher risk of allcause death or clinical deterioration with respect to patients with distal emboli, but this difference was not statistically significant (HR, 7.57; 95% CI, 0.95-60.16) (Fig 3). Bilateral PE was a risk factor for all-cause death or clinical deterioration only when associated with RVD. Saddle emboli were not
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Table 2—Symptoms at Presentation and Medical Conditions According to the Localization of Emboli Localization of Emboli Central Condition Dyspnea Chest pain Hemoptysis Tachycardia Hypotension Concomitant DVT Cancer COPD Obesity Immobilization Trauma Recent surgery Elevated serum troponin level RVD on echocardiography
Lobar
Distal
Bilateral
OR (95% CI)
P Value
OR (95% CI)
P Value
OR (95% CI)
P Value
OR (95% CI)
P Value
2.36 (1.44-3.86) 1.10 (0.73-1.64) 0.31 (0.90-1.03) 1.38 (0.93-2.05) 1.03 (0.60-1.78) 2.24 (1.41-3.55) 0.71 (0.46-1.09) 0.85 (0.46-1.55) 2.20 (0.97-5.02) 1.01 (0.55-1.84) 1.24 (0.58-2.66) 0.84 (0.37-1.88) 1.86 (1.31-2.65)
.001 ns ns ns ns .001 ns ns .06 ns ns ns .001
0.55 (0.32-0.94) 0.75 (0.47-1.21) 1.13 (0.30-4.26) 0.94 (0.60-1.50) 0.91 (0.50-1.67) 0.66 (0.40-1.10) 1.28 (0.80-2.06) 0.97 (0.48-1.93) 0.40 (0.14-1.17) 1.52 (0.80-2.90) 0.72 (0.29-1.80) 0.57 (0.19-1.70) 0.86 (0.58-1.27)
.03 ns ns ns ns ns ns ns .09 ns ns ns ns
0.52 (0.29-0.95) 1.26 (0.74-2.13) 2.80 (0.82-9.56) 0.57 (0.33-0.99) 1.04 (0.49-2.19) 0.43 (0.24-0.75) 1.27 (0.72-2.23) 1.44 (0.68-3.04) 0.56 (0.17-1.90) 0.47 (0.16-1.35) 1.12 (0.41-3.04) 2.37 (0.96-5.89) 0.34 (0.20-0.58)
.03 ns ns .05 ns .003 ns ns ns ns ns ns .001
3.12 (1.82-5.35) 1.00 (0.61-1.65) 0.32 (0.10-1.03) 1.67 (1.00-2.79) 1.10 (0.58-2.07) 1.61 (0.96-2.69) 0.80 (0.49-1.32) 0.89 (0.45-1.79) 4.55 (1.07-19.42) 0.85 (0.42-1.70) 1.92 (0.65-5.64) 0.56 (0.24-1.34) 2.62 (1.66-4.13)
.001 ns ns .05 ns ns ns ns .04 ns ns ns .001
4.04 (2.81-5.83)
.001
0.49 (0.32-0.72)
.001
0.18 (0.10-0.32)
.001
4.68 (2.95-7.43)
.001
ns 5 not significant. See Table 1 legend for expansion of other abbreviation.
predictors of all-cause death or clinical deterioration (HR, 1.42; 95% CI, 0.62-3.27; P not significant). The incidence of all-cause death in the overall study population was 6.2%, 9.5%, and 3.7% in patients with central, lobar, and distal emboli, respectively (5.3%, 6.6%, and 2.6% in the hemodynamically stable patients, respectively). A nonsignificant association was observed between central emboli and all-cause death
in the overall study population (HR, 2.79; 95% CI, 0.54-14.40) as well as in the initially hemodynamically stable patients (HR, 7.03; 95% CI, 0.82-59.98). Pulmonary Artery OI The OI was measured in 448 patients; 404 (90%) were hemodynamically stable. The mean OI was
0,10
Central PE Lobar PE Distal PE
Cumulative Hazard
0,08
0,06
0,04
0,02
0,00 0
5
10
15
20
25
30
days Figure 2. Cumulative risk of death or clinical deterioration in the overall study population. PE 5 pulmonary embolism. 1420
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0,08
Central PE Lobar PE
0,07
Distal PE
Cumulative Hazard
0,06 0,05 0,04 0,03 0,02 0,01 0,00 0
5
10
15
20
25
30
days Figure 3. Cumulative risk of death or clinical deterioration in hemodynamically stable patients. See Figure 2 legend for expansion of abbreviation.
33% ⫾ 19%, and the intraclass correlation coefficient was 0.67. No correlation was found between OI and sex or age. Mean OI was significantly higher in patients with dyspnea (35% ⫾ 19% vs 23% ⫾ 16%, P , .001), tachycardia (37% ⫾ 19% vs 30% ⫾ 18%, P , .001), and obesity (44% ⫾ 14% vs 33 ⫾ 19%, P 5 .004) than in patients without. OI was significantly lower in patients with hemoptysis (19% ⫾ 14% vs 33% ⫾ 19%, P 5 .009) or with a history of cancer (30% ⫾ 19% vs 34% ⫾ 19%, P 5 .05). No significant difference was shown in the mean OI values in patients with or without hypotension or chest pain and in patients with or without specific medical conditions (COPD, trauma, immobilization, previous DVT, diabetes, hypertension, autoimmune disease, or surgery). OI was significantly higher in patients with elevated levels of serum troponin (40% ⫾ 17% vs 29% ⫾ 19%, P , .001) as well as in patients with RVD on echocardiography (40% ⫾ 17% vs 24% ⫾ 17% P , .001). The mean OI values were similar in patients who died or had clinical deterioration at 30 days compared with those who had a favorable prognosis (33% ⫾ 19% vs 33% ⫾ 19%, P not significant). OI was not associated with all-cause death or clinical deterioration in the initially hemodynamically stable patients (34% ⫾ 18% vs 33% ⫾ 19%, P not significant). The distribution of all-cause death or clinical deterioration with respect to OI values is shown in Figure 4. No association was observed between OI and all-cause death in the overall study population (32% ⫾ 18%
vs 33% ⫾ 19%, P not significant) as well as in the initially hemodynamically stable patients (31% ⫾ 18% vs 33% ⫾ 19%, P not significant) (Table 3).
Discussion This study shows that the localization of emboli as assessed by MDCT angiography can be used for risk stratification in patients with acute PE who are hemodynamically stable. In these patients, the presence of emboli in the main pulmonary arteries is an independent determinant of all-cause death or clinical deterioration. Segmental or subsegmental emboli are associated with a relatively low risk of adverse clinical outcome. Risk stratification is recommended in hemodynamically stable patients with acute PE to identify those at low or intermediate risk for adverse outcomes.2 Low-risk patients are candidates for an early discharge or even home treatment, whereas intermediate-risk patients should be admitted to the hospital and considered for an upgrade in treatment.2,6 The results of this study further support the use of MDCT angiography as a single test for both diagnosis and risk stratification in patients with PE. As reported, right ventricular dilation on MDCT scan is associated with an adverse outcome.4,5 Both the localization of the emboli and the right ventricular dilation are rapidly achieved on MDCT scan and have the potential to be integrated into clinical models for risk
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Figure 4. Distribution of death or clinical deterioration according to OI values. See Figure 1 legend for expansion of abbreviation.
stratification in the ED.15 These findings could be of substantial clinical value because MDCT scan is the current standard test used in the diagnosis of PE worldwide. In the present study, the localization of emboli on MDCT scan does not seem to improve the risk stratification in the overall population of patients with PE. As a further observation, saddle emboli were not associated with 30-day mortality, thus confirming the results of a previous study.16 A nonsignificant association was found between mortality and central localization in both the overall study population and the patients who were initially normotensive. However, these results could have been influenced by the small number of events.
Also in the present study, central PE was found in 60% of the patients. Previous studies reported lower proportions of central PEs (about 30%).10 It is conceivable that the selection of recruiting centers (three cardiology units, two EDs, and four internal medicine wards) could have led to the inclusion of a greater proportion of high-risk patients in the study. We found no correlation between OI, as assessed by the Qanadli score, and mortality or clinical deterioration. This correlation has been a matter of debate for several years.7-9,17-20 The discordant findings obtained in different studies not only may be due to differences in the patient populations but also may reflect the low reproducibility and the high interobserver variability of this score. The large number of patients
Table 3—All-Cause Death or Clinical Deterioration According to Hemodynamic Status and MDCT Scan Findings Clinical Outcome and MDCT Scan Central localization All-cause death or clinical deterioration All-cause death Obstruction index All-cause death or clinical deterioration,a % Yes No All-cause death,a % Yes No
Overall Population (N 5 579)
Hemodynamically Stable Patients (n 5 516)
2.42 (0.77-7.59) 2.79 (0.54-14.40)
8.3 (1.0-67) 7.03 (0.82-59.98)
33 ⫾ 19 33 ⫾ 19
34 ⫾ 18 33 ⫾ 19
32 ⫾ 18 33 ⫾ 19
31 ⫾ 18 33 ⫾ 19
Data are presented as hazard ratio (95% CI) or mean ⫾ SD. MDCT 5 multidetector CT. aAll P values not significant. 1422
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evaluated in the present study as well as the central blinded assessment of OI strengthens the finding on the low clinical value of the OI. The OI was related to RVD on echocardiography and not to hemodynamic status. These findings reinforce the concept that in patients with acute PE, the hemodynamic status depends not only on PE-related factors, such as RVD on echocardiography and the embolic burden, but also on patient characteristics, such as age and comorbidities. In the present study, age . 75 years was a predictor of all-cause death or clinical deterioration in the overall study population and in the hemodynamically stable patients. We observed a correlation between RVD on echocardiography and central emboli, which is in line with a recent small study.21 We also found that OI was significantly higher in patients with RVD, but it was not a predictor of adverse outcome. The present study has some limitations. Although it was a prospective observational study, 35 patients were excluded mainly because of the lack of 30-day follow-up data or the unavailability of MDCT angiography for central assessment. Moreover, because of technical problems with CT transmission, MDCT angiography data from one study center were only suitable for the assessment of localization of emboli and not for the assessment of OI. We conclude that central localization of the emboli is a predictor of all-cause death or clinical deterioration in patients with acute PE who are hemodynamically stable. Taking into account even the results achieved with MDCT scan-detected right ventricular dilation, further management studies should evaluate the clinical value of risk stratification models exclusively based on MDCT scan findings. Acknowledgments Author contributions: Dr Vedovati had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Dr Vedovati: contributed to the conception and design of the study, acquisition of data, analysis and interpretation of data, and drafting of the article. Dr Becattini: contributed to the conception and design of the study, acquisition of data, analysis and interpretation of data, and drafting of the article. Dr Agnelli: contributed to the conception and design of the study, acquisition of data, analysis and interpretation of data, and drafting of the article. Dr Kamphuisen: contributed to the acquisition and interpretation of data and critical revision of the manuscript for important intellectual content. Dr Masotti: contributed to the acquisition and interpretation of data and critical revision of the manuscript for important intellectual content. Dr Pruszczyk: contributed to the acquisition and interpretation of data and critical revision of the manuscript for important intellectual content. Dr Casazza: contributed to the acquisition and interpretation of data and critical revision of the manuscript for important intellectual content.
Dr Salvi: contributed to the acquisition and interpretation of data and critical revision of the manuscript for important intellectual content. Dr Grifoni: contributed to the acquisition and interpretation of data and critical revision of the manuscript for important intellectual content. Dr Carugati: contributed to the acquisition and interpretation of data and critical revision of the manuscript for important intellectual content. Dr Konstantinides: contributed to the acquisition and interpretation of data and critical revision of the manuscript for important intellectual content. Dr Schreuder: contributed to the acquisition and interpretation of data and critical revision of the manuscript for important intellectual content. Dr Golebiowski: contributed to the acquisition and interpretation of data and critical revision of the manuscript for important intellectual content. Dr Duranti: contributed to the conception and design of the study, acquisition of data, analysis and interpretation of data, and drafting of the article. Financial/nonfinancial disclosures: The authors have reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article. Other contributions: The study was performed in nine centers. Six were in Italy (Department of Internal and Cardiovascular Medicine–Stroke Unit, S Maria della Misericordia Hospital, Perugia; Department of Internal Medicine, Cecina Hospital, Cecina; Department of Cardiology, San Carlo Borromeo Hospital, Milan; Department of Emergency Medicine, Ancona Hospital, Ancona; Department of Emergency Medicine, Careggi Hospital, Florence; and Department of Internal Medicine, Valduce Hospital, Como), one in Poland (Department of Internal Medicine and Cardiology, Warsaw Medical University), one in Germany (Department of Cardiology and Pulmonology, University of Göttingen, Göttingen), and one in The Netherlands (Department of Vascular Medicine, University Medical Center Groningen, Groningen). We thank the following participants who contributed to the study: Maciej Kostrubiec, MD, Department of Internal Medicine and Cardiology, Warsaw Medical University, Poland; Paola Mariani, MD, Ospedale San Carlo, Milano, Italy; Simone Vanni, MD, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy; Mareike Lankeit, MD, Department of Cardiology and Pulmonology, University of Göttingen, Göttingen, Germany; Cinzia Nitti, MD, Azienda Ospedaliera-Universitaria, Ancona, Italy; and Marina Bianchi, MD, Valduce Hospital, Como, Italy. Additional information: The e-Appendix can be found in the ”Supplemental Materials” area of the online article.
References 1. Agnelli G, Becattini C. Acute pulmonary embolism. N Engl J Med. 2010;363(3):266-274. 2. Torbicki A, Perrier A, Konstantinides S, et al; ESC Committee for Practice Guidelines (CPG). Guidelines on the diagnosis and management of acute pulmonary embolism: the Task Force for the Diagnosis and Management of Acute Pulmonary Embolism of the European Society of Cardiology (ESC). Eur Heart J. 2008;29(18):2276-2315. 3. Sanchez O, Trinquart L, Colombet I, et al. Prognostic value of right ventricular dysfunction in patients with haemodynamically stable pulmonary embolism: a systematic review. Eur Heart J. 2008;29(12):1569-1577. 4. Becattini C, Agnelli G, Vedovati MC, et al. Multidetector computed tomography for acute pulmonary embolism: diagnosis and risk stratification in a single test. Eur Heart J. 2011; 32(13):1657-1663. 5. Schoepf UJ, Kucher N, Kipfmueller F, Quiroz R, Costello P, Goldhaber SZ. Right ventricular enlargement on chest computed tomography: a predictor of early death in acute pulmonary embolism. Circulation. 2004;110(20):3276-3280.
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6. Jaff MR, McMurtry MS, Archer SL, et al; American Heart Association Council on Cardiopulmonary, Critical Care, Perioperative and Resuscitation; American Heart Association Council on Peripheral Vascular Disease; American Heart Association Council on Arteriosclerosis, Thrombosis and Vascular Biology. Management of massive and submassive pulmonary embolism, iliofemoral deep vein thrombosis, and chronic thromboembolic pulmonary hypertension: a scientific statement from the American Heart Association. Circulation. 2011;123(16):1788-1830. 7. Qanadli SD, El Hajjam M, Vieillard-Baron A, et al. New CT index to quantify arterial obstruction in pulmonary embolism: comparison with angiographic index and echocardiography. AJR Am J Roentgenol. 2001;176(6):1415-1420. 8. van der Meer RW, Pattynama PMT, van Strijen MJL, et al. Right ventricular dysfunction and pulmonary obstruction index at helical CT: prediction of clinical outcome during 3-month follow-up in patients with acute pulmonary embolism. Radiology. 2005;235(3):798-803. 9. Subramaniam RM, Mandrekar J, Chang C, et al. Pulmonary embolism outcome: a prospective evaluation of CT pulmonary angiographic clot burden score and ECG score. AJR Am J Roentgenol. 2008;190(6):1599-1604. 10. Klok FA, Djurabi RK, Nijkeuter M, et al. High D-dimer level is associated with increased 15-d and 3 months mortality through a more central localization of pulmonary emboli and serious comorbidity. Br J Haematol. 2008;140(2): 218-222. 11. Ghanima W, Abdelnoor M, Holmen LO, Nielssen BE, Ross S, Sandset PM. D-dimer level is associated with the extent of pulmonary embolism. Thromb Res. 2007;120(2):281-288. 12. Jeebun V, Doe SJ, Singh L, Worthy SA, Forrest IA. Are clinical parameters and biomarkers predictive of severity of acute pulmonary emboli on CTPA? QJM. 2010;103(2):91-97.
13. Konstantinides S, Geibel A, Heusel G, Heinrich F, Kasper W; Management Strategies and Prognosis of Pulmonary Embolism-3 Trial Investigators. Heparin plus alteplase compared with heparin alone in patients with submassive pulmonary embolism. N Engl J Med. 2002;347(15):1143-1150. 14. Kostrubiec M, Pruszczyk P, Bochowicz A, et al. Biomarkerbased risk assessment model in acute pulmonary embolism. Eur Heart J. 2005;26(20):2166-2172. 15. Jiménez D, Aujesky D, Moores L, et al; RIETE Investigators. Simplification of the Pulmonary Embolism Severity Index for prognostication in patients with acute symptomatic pulmonary embolism. Arch Intern Med. 2010;170(15): 1383-1389. 16. Pruszczyk P, Pacho R, Ciurzynski M, et al. Short term clinical outcome of acute saddle pulmonary embolism. Heart. 2003;89(3):335-336. 17. Araoz PA, Gotway MB, Harrington JR, Harmsen WS, Mandrekar JN. Pulmonary embolism: prognostic CT findings. Radiology. 2007;242(3):889-897. 18. Ghuysen A, Ghaye B, Willems V, et al. Computed tomographic pulmonary angiography and prognostic significance in patients with acute pulmonary embolism. Thorax. 2005;60(11):956-961. 19. Findik S, Erkan L, Light RW, Uzun O, Atici AG, Akan H. Massive pulmonary emboli and CT pulmonary angiography. Respiration. 2008;76(4):403-412. 20. Nural MS, Elmali M, Findik S, et al. Computed tomographic pulmonary angiography in the assessment of severity of acute pulmonary embolism and right ventricular dysfunction. Acta Radiol. 2009;50(6):629-637. 21. Berghaus TM, Haeckel T, Behr W, Wehler M, von Scheidt W, Schwaiblmair M. Central thromboembolism is a possible predictor of right heart dysfunction in normotensive patients with acute pulmonary embolism. Thromb Res. 2010;126(3): e201-e205.
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Original Research PULMONARY VASCULAR DISEASE
Multidetector CT Scan for Acute Pulmonary Embolism Embolic Burden and Clinical Outcome Maria Cristina Vedovati, MD; Cecilia Becattini, MD; Giancarlo Agnelli, MD; Pieter W. Kamphuisen, MD; Luca Masotti, MD; Piotr Pruszczyk, MD; Franco Casazza, MD; Aldo Salvi, MD; Stefano Grifoni, MD; Anna Carugati, MD; Stavros Konstantinides, MD; Marthe Schreuder, MD; Marek Golebiowski, MD; and Michele Duranti, MD
Background: In patients with acute pulmonary embolism (PE), the correlation between the embolic burden assessed by multidetector CT (MDCT) scan and clinical outcomes remains unclear. Patients with symptomatic acute PE diagnosed based on MDCT angiography were included in a multicenter study aimed at assessing the prognostic role of the embolic burden evaluated with MDCT scan. Methods: Embolic burden was assessed as (1) localization of the emboli as central (saddle or at least one main pulmonary artery), lobar, or distal (segmental or subsegmental arteries) and (2) the obstruction index by the scoring system of Qanadli. The primary outcome was 30-day all-cause death or clinical deterioration. Predictors of all-cause death or clinical deterioration were identified by Cox regression statistics. Results: Overall, 579 patients were included in the study; 60 (10.4%) died or had clinical deterioration at 30 days. Central localization of emboli was not associated with all-cause death or clinical deterioration (hazard ratio [HR], 2.42; 95% CI, 0.77-7.59; P 5 .13). However, in 516 hemodynamically stable patients, central localization of emboli (HR, 8.3; 95% CI, 1.0-67; P 5 .047) was an independent predictor of all-cause death or clinical deterioration, whereas distal emboli were inversely associated with these outcome events (HR, 0.12; 95% CI, 0.015-0.97; P 5 .047). No correlation was found between obstruction index (evaluated in 448 patients) and all-cause death or clinical deterioration in the overall study population and in the hemodynamically stable patients. Conclusions: In hemodynamically stable patients with acute PE, central emboli are associated with an increased risk for all-cause death or clinical deterioration. This risk is low in patients with segmental or subsegmental PE. CHEST 2012; 142(6):1417–1424 Abbreviations: HR 5 hazard ratio; MDCT 5 multidetector CT; OI 5 obstruction index; PE 5 pulmonary embolism; RVD 5 right ventricle dysfunction
pulmonary embolism (PE) is a potentially Acute fatal disease with a wide spectrum of clinical pre-
sentations. Risk stratification is recommended for driving the clinical management of patients with acute PE.1,2 In hemodynamically stable patients, risk stratification is mainly based on the evaluation of markers of myocardial injury (elevated serum troponin level) and myocardial dysfunction (right ventricle dysfunction [RVD]). The presence of RVD on echocardiography is associated with an increased risk for in-hospital mortality (risk ratio, 2.5; 95% CI, 1.2-5.5).3
Multidetector CT (MDCT) angiography is the most commonly used procedure for the diagnosis of PE. By visualizing the heart chambers and allowing the assessment of RVD, MDCT scan has the potential to contribute to prognostic stratification of patients with PE.4,5 In the most recent guidelines of the European Society of Cardiology and of the American Heart Association, hemodynamic status and markers of myocardial dysfunction or injury replaced the burden of emboli on pulmonary angiography for the stratification
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of severity of PE.2,6 Studies evaluated the prognostic value of the burden of emboli as assessed by MDCT scan in patients with acute PE.7-11 The burden of emboli has been assessed by MDCT angiography as the localization of emboli in different branches of the pulmonary artery10-12 or as a global estimate of the degree of obstruction (obstruction index [OI]).7-9 However, the correlation between the localization of the emboli or the OI assessed by MDCT angiography and the clinical outcome remains unclear. We performed a multicenter study aimed at assessing the prognostic role of the localization of the emboli and of the OI evaluated by MDCT scan in patients with acute PE.
The primary study outcome was 30-day all-cause death or clinical deterioration both in the overall population and in hemodynamically stable patients with PE. Clinical deterioration was defined as the occurrence of one or more of the following events: shock (systemic systolic BP , 90 mm Hg or a drop by ⱖ 40 mm Hg for . 15 min with signs of peripheral hypoperfusion), need for rescue thrombolysis, endotracheal intubation, cathecholamine infusion, or CPR.13 Hemodynamic stability was defined as a value of systemic systolic BP . 90 mm Hg with no signs of peripheral hypoperfusion. In case of death, the presumed cause was reported. PE was considered the cause of death if it was confirmed on autopsy and in case of sudden death that could not be explained by a more compelling alternative diagnosis. The study was approved by local institutional review boards (Comitato Etico delle Aziende Sanitarie Umbre: 984/06). All patients gave written informed consent for inclusion in the study and for the data analysis. Data Collection
Materials and Methods Patients Patients with symptomatic acute PE by MDCT angiography were included in the study provided that data on 30-day follow-up were available. Patients with inadequate MDCT scans (poor imaging) were excluded. Any decision about treatment was at the discretion of the attending physician. Study Design This international, multicenter, prospective cohort study in patients with acute PE was performed in nine centers in Italy, Poland, Germany, and The Netherlands between October 2008 and May 2010. Inpatients from cardiology, emergency, or internal medicine departments were included. The study was aimed at assessing the prognostic value of (1) the localization of the emboli and (2) the burden of emboli (measured as OI) as detected by MDCT angiography. Manuscript received November 4, 2011; revision accepted April 1, 2012. Affiliations: From the Internal and Cardiovascular Medicine– Stroke Unit (Drs Vedovati, Becattini, and Agnelli), University of Perugia, and Department of Radiology (Dr Duranti), S Maria della Misericordia Hospital, Perugia, Italy; Department of Vascular Medicine (Drs Kamphuisen and Schreuder), University Medical Center Groningen, Groningen, The Netherlands; Department of Internal Medicine (Dr Masotti), Cecina Hospital, Cecina, Italy; Department of Internal Medicine and Cardiology (Dr Pruszczyk) and Department of Radiology (Dr Golebiowski), Warsaw Medical University, Warsaw, Poland; Department of Cardiology (Dr Casazza), San Carlo Borromeo Hospital, Milan, Italy; Department of Emergency Medicine (Dr Salvi), Ancona Hospital, Ancona, Italy; Department of Emergency Medicine (Dr Grifoni), Careggi Hospital, Florence, Italy; Department of Internal Medicine (Dr Carugati), Valduce Hospital, Como, Italy; and Department of Cardiology (Dr Konstantinides), Democritus University of Thrace, Alexandroupolis, Greece. Funding/Support: The authors have reported to CHEST that no funding was received for this study. Correspondence to: Maria Cristina Vedovati, MD, Internal and Cardiovascular Medicine–Stroke Unit, via G. Dottori, S. Maria della Misericordia Hospital, 06123 Perugia, Italy; e-mail: [email protected] © 2012 American College of Chest Physicians. Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details. DOI: 10.1378/chest.11-2739
For all patients, the following data were collected: demographic features (age, sex), clinical presentation (signs, symptoms, hemodynamic status, etc), medical history (cancer, COPD, congestive heart failure, etc), laboratory (serum troponin levels) and echocardiographic findings (RVD), anticoagulant treatment, and clinical outcome. Serum troponin level was considered elevated or normal based on local assays and cutoff values. The diagnosis of RVD required the presence of at least two of the following: right-to-left ventricular end-diastolic diameter ratio . 0.9 in the apical four-chamber view, right-to-left ventricular end-diastolic diameter ratio . 0.7 in the parasternal long-axis or subcostal fourchamber views, paradoxical interventricular septal motion, or systolic pulmonary artery pressure . 30 mm Hg.2-4,14 MDCT Angiography Standard contrast-enhanced protocols for the diagnosis of PE were used. See e-Appendix 1 for a list of the CT scanners used at each study location. Standardized dose rate and total dose of contrast medium were used. Image acquisition was started with a scanning delay of 15 to 20 s after the start of the IV injection of contrast medium. MDCT scans were recorded on CDs and centrally assessed for both localization and burden of emboli. The localization of the emboli was evaluated and categorized as follows: central (saddle or at least one main pulmonary artery), lobar (at least one lobar artery), distal (segmental or subsegmental pulmonary arteries), monolateral, or bilateral. The OI was calculated according to the scoring system of Qanadli.7 The score was calculated as N 3 D, where N is the value of the proximal clot site equal to the number of segmental branches arising distally, and D is the degree of obstruction score distinguished as partial (value 5 1) or total (value 5 2). The maximum score is 40 (thrombus completely obstructing the main pulmonary artery), which corresponds to an OI of 100%. Localization of the emboli and OI were centrally determined by a panel comprising a radiologist (M. D.) and at least two of three internal medicine physicians (M. C. V., C. B., and M. S.), who were unaware of the clinical status and outcome. Statistical Analysis Data are reported as proportions or as mean ⫾ SD. Student t test was used for comparisons of continuous data between groups, and x2 test was used for comparisons of dichotomous variables. P , .05 indicates statistical significance in all the analyses. All P values are two sided. Cox regression analysis was used to assess predictors of all-cause death or clinical deterioration. Results are reported as hazard ratios (HRs) and 95% CIs. The following variables were considered in the multivariable analysis:
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demographic features (age, sex), comorbidity (cancer), laboratory findings (serum troponin level), RVD on echocardiography, and CT scan findings. Assumption of proportional hazard was assessed and satisfied by visual inspection of the log-minus-log survival curves for localization of emboli. Interobserver agreement was tested by the intraclass correlation coefficient or the k coefficient. All analyses were performed using SPSS, version 11.0 (IBM) statistical software.
Results Overall, 614 patients with acute symptomatic MDCT scan-confirmed PE were evaluated, and 579 patients were included in the study. The flow diagram for inclusion in the study is shown in Figure 1. Five hundred sixteen patients (89%) were hemodynamically stable at admission. Mean age was 69 ⫾ 16 years (range, 18-98 years), and 47.7% were men. Patient characteristics are shown in Table 1. During the 30-day follow-up period, 60 patients (10.4%) died or had clinical deterioration. Thirty-four patients (5.9%) died, of whom 17 (2.9%) died presumably of PE. Localization of the Emboli Localization of emboli was central in 348 patients (60%), lobar in 144 (25%), and distal in 87 (15%). Saddle emboli were observed in 78 (13.5%) and subsegmental emboli in 27 (4.8%). PE was bilateral in 446 (77%). The k index for interobserver agreement was 0.82. No correlation was found between the localization of emboli and age or sex. Dyspnea, concomitant DVT, and obesity were significantly more common in patients with than in patients without a central localization of the emboli (Table 2). Distal emboli were inversely associated with dyspnea, tachycardia, or concomitant DVT. Bilateral PE was associated with dyspnea, tachycardia, and obesity. Elevated levels of serum troponin and the presence of RVD at echocardiography were more common in patients with central or bilateral emboli (Table 2). An inverse association was found
Figure 1. Flow diagram for inclusion in the study. MDCT 5 multidetector CT; OI 5 obstruction index.
Table 1—Characteristics of the Study Population Characteristic
Value
Male sex Age, y Risk factors Concomitant DVT Obesity Cancer Immobilization Trauma Recent surgery COPD Symptoms at presentation Dyspnea Chest pain Hemoptysis Tachycardia Elevated serum troponin level RVD at echocardiography Thrombolytic treatment
276 (47.7) 68.5 ⫾ 16.3 417 (72.0) 48 (8.3) 123 (21.2) 71 (12.3) 44 (7.6) 28 (4.8) 60 (10.4) 473 (81.7) 212 (36.6) 16 (2.8) 243 (42.0) 261 (45.0) 302 (52.2) 41(7.1)
Data are presented as No. (%) or mean ⫾ SD. RVD 5 right ventricle dysfunction.
between distal emboli and elevated levels of serum troponin or RVD on echocardiography. The incidence of all-cause death or clinical deterioration was 11.2%, 11.1%, and 5.7% in patients with central, lobar, and distal emboli, respectively. At multivariate analysis, no association was found between localization of emboli and all-cause death or clinical deterioration in the overall population (central emboli HR, 2.42; 95% CI, 0.77-7.59; lobar emboli HR, 2.15; 95% CI, 0.70-6.55; distal emboli HR, 0.41; 95% CI, 0.13-1.30; all P not significant) (Fig 2). Age . 75 years (HR, 1.72; 95% CI, 1.01-2.94; P 5 .046), RVD on echocardiography (HR, 2.57; 95% CI, 1.36-4.89; P 5 .004), and hypotension at presentation (HR, 5.08; 95% CI, 2.97-8.69; P , .001) were independent predictors of adverse outcome. When the analysis was restricted to the 516 initially hemodynamically stable patients, the rate of all-cause death or clinical deterioration was 8.4%, 7.8%, and 2.6% in patients with central, lobar, and distal emboli, respectively. In these patients, central emboli (HR, 8.3; 95% CI, 1.0-67; P 5 .047), age . 75 years (HR, 2.6; 95% CI, 1.3-5.2; P 5 .008), and RVD on echocardiography (HR, 2.4; 95% CI, 1.1-5.2; P 5 .029) were independent predictors of all-cause death or clinical deterioration (Fig 3). Distal localization of emboli was associated with a reduced risk for these outcome events (HR, 0.12; 95% CI, 0.01-0.97; P 5 .047). Patients with lobar emboli had a higher risk of allcause death or clinical deterioration with respect to patients with distal emboli, but this difference was not statistically significant (HR, 7.57; 95% CI, 0.95-60.16) (Fig 3). Bilateral PE was a risk factor for all-cause death or clinical deterioration only when associated with RVD. Saddle emboli were not
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Table 2—Symptoms at Presentation and Medical Conditions According to the Localization of Emboli Localization of Emboli Central Condition Dyspnea Chest pain Hemoptysis Tachycardia Hypotension Concomitant DVT Cancer COPD Obesity Immobilization Trauma Recent surgery Elevated serum troponin level RVD on echocardiography
Lobar
Distal
Bilateral
OR (95% CI)
P Value
OR (95% CI)
P Value
OR (95% CI)
P Value
OR (95% CI)
P Value
2.36 (1.44-3.86) 1.10 (0.73-1.64) 0.31 (0.90-1.03) 1.38 (0.93-2.05) 1.03 (0.60-1.78) 2.24 (1.41-3.55) 0.71 (0.46-1.09) 0.85 (0.46-1.55) 2.20 (0.97-5.02) 1.01 (0.55-1.84) 1.24 (0.58-2.66) 0.84 (0.37-1.88) 1.86 (1.31-2.65)
.001 ns ns ns ns .001 ns ns .06 ns ns ns .001
0.55 (0.32-0.94) 0.75 (0.47-1.21) 1.13 (0.30-4.26) 0.94 (0.60-1.50) 0.91 (0.50-1.67) 0.66 (0.40-1.10) 1.28 (0.80-2.06) 0.97 (0.48-1.93) 0.40 (0.14-1.17) 1.52 (0.80-2.90) 0.72 (0.29-1.80) 0.57 (0.19-1.70) 0.86 (0.58-1.27)
.03 ns ns ns ns ns ns ns .09 ns ns ns ns
0.52 (0.29-0.95) 1.26 (0.74-2.13) 2.80 (0.82-9.56) 0.57 (0.33-0.99) 1.04 (0.49-2.19) 0.43 (0.24-0.75) 1.27 (0.72-2.23) 1.44 (0.68-3.04) 0.56 (0.17-1.90) 0.47 (0.16-1.35) 1.12 (0.41-3.04) 2.37 (0.96-5.89) 0.34 (0.20-0.58)
.03 ns ns .05 ns .003 ns ns ns ns ns ns .001
3.12 (1.82-5.35) 1.00 (0.61-1.65) 0.32 (0.10-1.03) 1.67 (1.00-2.79) 1.10 (0.58-2.07) 1.61 (0.96-2.69) 0.80 (0.49-1.32) 0.89 (0.45-1.79) 4.55 (1.07-19.42) 0.85 (0.42-1.70) 1.92 (0.65-5.64) 0.56 (0.24-1.34) 2.62 (1.66-4.13)
.001 ns ns .05 ns ns ns ns .04 ns ns ns .001
4.04 (2.81-5.83)
.001
0.49 (0.32-0.72)
.001
0.18 (0.10-0.32)
.001
4.68 (2.95-7.43)
.001
ns 5 not significant. See Table 1 legend for expansion of other abbreviation.
predictors of all-cause death or clinical deterioration (HR, 1.42; 95% CI, 0.62-3.27; P not significant). The incidence of all-cause death in the overall study population was 6.2%, 9.5%, and 3.7% in patients with central, lobar, and distal emboli, respectively (5.3%, 6.6%, and 2.6% in the hemodynamically stable patients, respectively). A nonsignificant association was observed between central emboli and all-cause death
in the overall study population (HR, 2.79; 95% CI, 0.54-14.40) as well as in the initially hemodynamically stable patients (HR, 7.03; 95% CI, 0.82-59.98). Pulmonary Artery OI The OI was measured in 448 patients; 404 (90%) were hemodynamically stable. The mean OI was
0,10
Central PE Lobar PE Distal PE
Cumulative Hazard
0,08
0,06
0,04
0,02
0,00 0
5
10
15
20
25
30
days Figure 2. Cumulative risk of death or clinical deterioration in the overall study population. PE 5 pulmonary embolism. 1420
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0,08
Central PE Lobar PE
0,07
Distal PE
Cumulative Hazard
0,06 0,05 0,04 0,03 0,02 0,01 0,00 0
5
10
15
20
25
30
days Figure 3. Cumulative risk of death or clinical deterioration in hemodynamically stable patients. See Figure 2 legend for expansion of abbreviation.
33% ⫾ 19%, and the intraclass correlation coefficient was 0.67. No correlation was found between OI and sex or age. Mean OI was significantly higher in patients with dyspnea (35% ⫾ 19% vs 23% ⫾ 16%, P , .001), tachycardia (37% ⫾ 19% vs 30% ⫾ 18%, P , .001), and obesity (44% ⫾ 14% vs 33 ⫾ 19%, P 5 .004) than in patients without. OI was significantly lower in patients with hemoptysis (19% ⫾ 14% vs 33% ⫾ 19%, P 5 .009) or with a history of cancer (30% ⫾ 19% vs 34% ⫾ 19%, P 5 .05). No significant difference was shown in the mean OI values in patients with or without hypotension or chest pain and in patients with or without specific medical conditions (COPD, trauma, immobilization, previous DVT, diabetes, hypertension, autoimmune disease, or surgery). OI was significantly higher in patients with elevated levels of serum troponin (40% ⫾ 17% vs 29% ⫾ 19%, P , .001) as well as in patients with RVD on echocardiography (40% ⫾ 17% vs 24% ⫾ 17% P , .001). The mean OI values were similar in patients who died or had clinical deterioration at 30 days compared with those who had a favorable prognosis (33% ⫾ 19% vs 33% ⫾ 19%, P not significant). OI was not associated with all-cause death or clinical deterioration in the initially hemodynamically stable patients (34% ⫾ 18% vs 33% ⫾ 19%, P not significant). The distribution of all-cause death or clinical deterioration with respect to OI values is shown in Figure 4. No association was observed between OI and all-cause death in the overall study population (32% ⫾ 18%
vs 33% ⫾ 19%, P not significant) as well as in the initially hemodynamically stable patients (31% ⫾ 18% vs 33% ⫾ 19%, P not significant) (Table 3).
Discussion This study shows that the localization of emboli as assessed by MDCT angiography can be used for risk stratification in patients with acute PE who are hemodynamically stable. In these patients, the presence of emboli in the main pulmonary arteries is an independent determinant of all-cause death or clinical deterioration. Segmental or subsegmental emboli are associated with a relatively low risk of adverse clinical outcome. Risk stratification is recommended in hemodynamically stable patients with acute PE to identify those at low or intermediate risk for adverse outcomes.2 Low-risk patients are candidates for an early discharge or even home treatment, whereas intermediate-risk patients should be admitted to the hospital and considered for an upgrade in treatment.2,6 The results of this study further support the use of MDCT angiography as a single test for both diagnosis and risk stratification in patients with PE. As reported, right ventricular dilation on MDCT scan is associated with an adverse outcome.4,5 Both the localization of the emboli and the right ventricular dilation are rapidly achieved on MDCT scan and have the potential to be integrated into clinical models for risk
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Figure 4. Distribution of death or clinical deterioration according to OI values. See Figure 1 legend for expansion of abbreviation.
stratification in the ED.15 These findings could be of substantial clinical value because MDCT scan is the current standard test used in the diagnosis of PE worldwide. In the present study, the localization of emboli on MDCT scan does not seem to improve the risk stratification in the overall population of patients with PE. As a further observation, saddle emboli were not associated with 30-day mortality, thus confirming the results of a previous study.16 A nonsignificant association was found between mortality and central localization in both the overall study population and the patients who were initially normotensive. However, these results could have been influenced by the small number of events.
Also in the present study, central PE was found in 60% of the patients. Previous studies reported lower proportions of central PEs (about 30%).10 It is conceivable that the selection of recruiting centers (three cardiology units, two EDs, and four internal medicine wards) could have led to the inclusion of a greater proportion of high-risk patients in the study. We found no correlation between OI, as assessed by the Qanadli score, and mortality or clinical deterioration. This correlation has been a matter of debate for several years.7-9,17-20 The discordant findings obtained in different studies not only may be due to differences in the patient populations but also may reflect the low reproducibility and the high interobserver variability of this score. The large number of patients
Table 3—All-Cause Death or Clinical Deterioration According to Hemodynamic Status and MDCT Scan Findings Clinical Outcome and MDCT Scan Central localization All-cause death or clinical deterioration All-cause death Obstruction index All-cause death or clinical deterioration,a % Yes No All-cause death,a % Yes No
Overall Population (N 5 579)
Hemodynamically Stable Patients (n 5 516)
2.42 (0.77-7.59) 2.79 (0.54-14.40)
8.3 (1.0-67) 7.03 (0.82-59.98)
33 ⫾ 19 33 ⫾ 19
34 ⫾ 18 33 ⫾ 19
32 ⫾ 18 33 ⫾ 19
31 ⫾ 18 33 ⫾ 19
Data are presented as hazard ratio (95% CI) or mean ⫾ SD. MDCT 5 multidetector CT. aAll P values not significant. 1422
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Original Research
evaluated in the present study as well as the central blinded assessment of OI strengthens the finding on the low clinical value of the OI. The OI was related to RVD on echocardiography and not to hemodynamic status. These findings reinforce the concept that in patients with acute PE, the hemodynamic status depends not only on PE-related factors, such as RVD on echocardiography and the embolic burden, but also on patient characteristics, such as age and comorbidities. In the present study, age . 75 years was a predictor of all-cause death or clinical deterioration in the overall study population and in the hemodynamically stable patients. We observed a correlation between RVD on echocardiography and central emboli, which is in line with a recent small study.21 We also found that OI was significantly higher in patients with RVD, but it was not a predictor of adverse outcome. The present study has some limitations. Although it was a prospective observational study, 35 patients were excluded mainly because of the lack of 30-day follow-up data or the unavailability of MDCT angiography for central assessment. Moreover, because of technical problems with CT transmission, MDCT angiography data from one study center were only suitable for the assessment of localization of emboli and not for the assessment of OI. We conclude that central localization of the emboli is a predictor of all-cause death or clinical deterioration in patients with acute PE who are hemodynamically stable. Taking into account even the results achieved with MDCT scan-detected right ventricular dilation, further management studies should evaluate the clinical value of risk stratification models exclusively based on MDCT scan findings. Acknowledgments Author contributions: Dr Vedovati had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Dr Vedovati: contributed to the conception and design of the study, acquisition of data, analysis and interpretation of data, and drafting of the article. Dr Becattini: contributed to the conception and design of the study, acquisition of data, analysis and interpretation of data, and drafting of the article. Dr Agnelli: contributed to the conception and design of the study, acquisition of data, analysis and interpretation of data, and drafting of the article. Dr Kamphuisen: contributed to the acquisition and interpretation of data and critical revision of the manuscript for important intellectual content. Dr Masotti: contributed to the acquisition and interpretation of data and critical revision of the manuscript for important intellectual content. Dr Pruszczyk: contributed to the acquisition and interpretation of data and critical revision of the manuscript for important intellectual content. Dr Casazza: contributed to the acquisition and interpretation of data and critical revision of the manuscript for important intellectual content.
Dr Salvi: contributed to the acquisition and interpretation of data and critical revision of the manuscript for important intellectual content. Dr Grifoni: contributed to the acquisition and interpretation of data and critical revision of the manuscript for important intellectual content. Dr Carugati: contributed to the acquisition and interpretation of data and critical revision of the manuscript for important intellectual content. Dr Konstantinides: contributed to the acquisition and interpretation of data and critical revision of the manuscript for important intellectual content. Dr Schreuder: contributed to the acquisition and interpretation of data and critical revision of the manuscript for important intellectual content. Dr Golebiowski: contributed to the acquisition and interpretation of data and critical revision of the manuscript for important intellectual content. Dr Duranti: contributed to the conception and design of the study, acquisition of data, analysis and interpretation of data, and drafting of the article. Financial/nonfinancial disclosures: The authors have reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article. Other contributions: The study was performed in nine centers. Six were in Italy (Department of Internal and Cardiovascular Medicine–Stroke Unit, S Maria della Misericordia Hospital, Perugia; Department of Internal Medicine, Cecina Hospital, Cecina; Department of Cardiology, San Carlo Borromeo Hospital, Milan; Department of Emergency Medicine, Ancona Hospital, Ancona; Department of Emergency Medicine, Careggi Hospital, Florence; and Department of Internal Medicine, Valduce Hospital, Como), one in Poland (Department of Internal Medicine and Cardiology, Warsaw Medical University), one in Germany (Department of Cardiology and Pulmonology, University of Göttingen, Göttingen), and one in The Netherlands (Department of Vascular Medicine, University Medical Center Groningen, Groningen). We thank the following participants who contributed to the study: Maciej Kostrubiec, MD, Department of Internal Medicine and Cardiology, Warsaw Medical University, Poland; Paola Mariani, MD, Ospedale San Carlo, Milano, Italy; Simone Vanni, MD, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy; Mareike Lankeit, MD, Department of Cardiology and Pulmonology, University of Göttingen, Göttingen, Germany; Cinzia Nitti, MD, Azienda Ospedaliera-Universitaria, Ancona, Italy; and Marina Bianchi, MD, Valduce Hospital, Como, Italy. Additional information: The e-Appendix can be found in the ”Supplemental Materials” area of the online article.
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Original Research