Thrombosis Research 133 (2014) 182–186

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Regular Article

Prognostic implications of computed tomographic right ventricular dilation in patients with acute pulmonary embolism Keum-Ju Choi a, Seung-Ick Cha a,⁎, Kyung-Min Shin b, Jaekwang Lim b, Seung-Soo Yoo a, Jaehee Lee a, Shin-Yup Lee a, Chang-Ho Kim a, Jae-Yong Park a, Won-Kee Lee c a b c

Department of Internal Medicine, Kyungpook National University School of Medicine,Daegu, Korea Department of Radiology, Kyungpook National University School of Medicine, Daegu, Korea Department of Preventive Medicine, Kyungpook National University School of Medicine, Daegu, Korea

a r t i c l e

i n f o

Article history: Received 17 September 2013 Received in revised form 13 November 2013 Accepted 22 November 2013 Available online 1 December 2013 Keywords: Computed tomography Prognosis Pulmonary embolism Right ventricular dysfunction

a b s t r a c t Introduction: Whether right ventricular (RV) dilation on computerized tomography (RVD-CT) is a useful predictor for clinical outcomes of acute pulmonary embolism (PE) remains debatable. Furthermore, data regarding the best combination of prognostic markers for predicting the adverse outcome of PE are limited. Materials and Methods: The authors retrospectively reviewed 657 consecutive patients hospitalized at a tertiary referral center with a diagnosis of PE based on multi-detector row CT scan. Results: Patients were allocated into an adverse outcome group (11% [n = 69]) or a low risk group (89% [n = 588]). Multivariate analysis showed that RVD-CT (RV/left ventricle [LV] diameter ratio ≥ 1), high pulmonary embolism severity index (PESI) score (class IV-V), high N-terminal-pro-B-type natriuretic peptide (NTproBNP,≥1,136 pg/ml), and elevated troponin I (≥ 0.05 ng/ml) significantly predicted an adverse outcome (odds ratio [OR] 6.26, 95% confidence interval [CI] 2.74-14.31, p b 0.001; OR 4.71, 95% CI 2.00-11.07, p b 0.001; OR 2.71, 95% CI 1.15-6.39, p = 0.023; and OR 3.00, 95% CI 1.27-7.07, p = 0.012, respectively). The addition of RVD-CT to PESI, NT-proBNP, troponin I or their combinations enhanced the positive predictive values and positive likelihood ratios of an adverse outcome. Conclusions: RVD-CT could be an independent prognostic factor of adverse outcomes in patients with acute PE, and provides additional prognostic value when combined with other prognostic factors. © 2013 Elsevier Ltd. All rights reserved.

Introduction Mortality rates of acute pulmonary embolism (PE) vary from less than 5% in clinically stable patients to more than 30% in hemodynamically unstable patients [1–4]. The main cause of early mortality is right ventricular (RV) failure, whereas most late deaths are caused by underlying diseases, such as cancer [5–7]. Risk stratification is pivotal for determining the therapeutic strategy for acute PE. To reduce PE-related mortality, high risk patients with hypotension and patients requiring more aggressive therapy than standard anticoagulation, such as thrombolytic therapy, should be promptly identified. The first step in clinical decision-making involves consideration of clinical variables, such as PE severity index (PESI) [8]. This index provides a validated means of making clinical predictions and is useful for identifying low risk patients suitable for outpatient therapy, but not for identifying high risk patients [9]. Furthermore, although RV

⁎ Corresponding author at: Department of Internal Medicine, Kyungpook National University Hospital, 130 Dongdeok-Ro, Jung-Gu, Daegu 700–721, South Korea. Tel.: +82 53 200 6412; fax: +82 53 426 2046. E-mail address: [email protected] (S.-I. Cha). 0049-3848/$ – see front matter © 2013 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.thromres.2013.11.020

dysfunction is directly associated with PE-related mortality, it is not incorporated in the PESI scoring system [9]. Therefore, it has been suggested that prognostic factors suggestive of RV dysfunction should be considered to improve predictability in high risk patients [10]. Recent studies on prognostic assessment of PE have focused on RV dysfunction and myocardial injury [10]. Furthermore, B-type natriuretic peptide (BNP) or N-terminal-pro-BNP (NT-proBNP) and troponin I or T, which are blood biomarkers of RV dysfunction, have been used in clinical research and practice [10]. At present, echocardiography remains the reference standard for assessing RV dysfunction in PE patients [11– 13], but it is of limited availability in many institutions, and occasionally its imaging quality is poor. Because the majority of patients with PE are diagnosed by multi-detector row computed tomography (MDCT), CT is a more accessible diagnostic method than echocardiography for detecting RV dysfunction in clinical practice [9]. Many reports have studied the utility of CT as a predictor of mortality in these patients [14–17], and of the various CT measurements examined, RV/left ventricle (LV) diameter ratio is the most promising [17]. However, whether RV dilation on CT (RVD-CT) is a useful predictor of poor prognosis remains debatable. Furthermore, combinations of prognostic factors, such as PESI, blood biomarkers, and CT parameters, are likely to be more predictive than any single factor. However, data regarding the best

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combination of prognostic factors for the prediction of mortality in PE are limited [18]. Thus, the aim of the present study was to assess whether RVD-CT could be used to predict clinical outcome in patients with PE. In addition, we investigated whether combinations of RVD-CT and other well-known markers could be used to improve prognostic value in terms of predicting adverse outcomes. Methods Study Population We retrospectively identified 657 consecutive patients hospitalized at Kyungpook National University Hospital (KNUH), a tertiary referral center, in Daegu, South Korea between March 2003 and December 2012 with a MDCT-based diagnosis of PE. Patients were allocated based on clinical outcome to an adverse outcome group or a low risk group. This study was approved by the Institutional Review Board of the KNUH, which waived the requirement for written informed consent because of the retrospective nature of the study. Clinical Outcome PE-related in-hospital death was defined as in-hospital death fulfilling the following criteria: if there were objective evidences of death directly caused by PE or if death could not be attributed to other causes and PE could not be excluded. Adverse outcome was defined as PE-related in-hospital death or serious clinical conditions, including infusion of vasopressors because of persistent hypotension, refractory hypoxia (impending respiratory failure or mechanical ventilation), or cardiopulmonary resuscitation, which is similar to the definitions used in previous studies [19,20]. Data Collection Demographic patient data, including age, gender, and body mass index (BMI) at presentation were checked, and risk factors of venous thromboembolism (VTE) and comorbid conditions were reviewed. Unprovoked PE was defined as the absence of reversible provoking risk factors, such as surgery, trauma, active cancer, pregnancy and puerperium within 3 months of the event, or immobilization (bed rest within past month for most of the day for ≥ 3 consecutive days) [21]. The presence of symptoms, hypotension (systolic blood pressure b 90 mm Hg), and tachycardia (heart rate N110/min) were also recorded. PESI was retrospectively calculated by a pulmonologist (C.K.J.) [8]. PESI score was obtained by summing each patient’s age (years), male (10 points), cancer (30 points), heart failure (10 points), chronic lung disease (10 points), pulse rate ≥110/min (20 points), systolic blood pressure b100 mmHg (30 points), respiratory rate ≥30/min (20 points), temperature b36 °C (20 points), altered mental status (60 points), and arterial oxygen saturation b90% (20 points). Each patient’s score correspond with the following risk classes: ≤65, class I (very low risk); 66–85, class II (low risk); 86–105, class III (intermediate risk); 106–125, class IV (high risk); N125, class V (very high risk).The usage of thrombolytic agents, VTE recurrence, and length of hospital stay were also checked. Blood levels of NT-proBNP and troponin I were checked, and arterial blood gas analysis (ABGA) data, including partial pressure of oxygen in arterial blood (PaO2), partial pressure of carbon dioxide in arterial blood (PaCO2 ), inspired oxygen fraction (FiO2 ), and PaO2/FiO2 ratio were recorded. Eletrocardiographic (ECG) changes were reviewed for the presence of T-wave inversion on precordial leads, Q1S3T3, and right bundle branch block. Transthoracic echocardiographic findings including the presence of RV dysfunction and RV systolic pressure (RVSP) were also reviewed. RV dysfunction was defined echocardiographically as RV free wall hypokinesia, and

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RVSPs were calculated using TR flow velocity as determined by Doppler echocardiography [22]. Radiological Evaluation CT scans were performed using a MDCT with 16 or 64 detector rows (Light Speed 16, General Electric, Milwaukee, WI, USA; or Aquilion 64, Toshiba Medical Systems, Japan). As described in an earlier study [23], PE was diagnosed on CT images as a sharply delineated pulmonary arterial filling defect present in at least two consecutive image sections, either located centrally within the vessel or with acute angles at its interface with the vessel wall. RV diameter was measured in the transverse section that showed the tricuspid valve at its widest from the inner wall to the inner wall [15]. Left ventricle (LV) diameter was measured on the transverse image that showed the mitral valve at its widest like the diameter of RV. The RV/LV diameter ratios were calculated (Fig. 1). The most proximal sites of pulmonary arteries where pulmonary emboli were observed were also recorded. Statistical Analysis Statistical analysis was performed using SPSS, version 12.0 (SPSS Inc., Chicago, IL, USA). Data were expressed as medians with interquartile ranges (IQR) for continuous variables and numbers with percentages for categorical variables. The Mann–Whitney U test was used to compare continuous variables between the adverse outcome and low risk groups, and chi-squared test or Fisher’s exact test was used to compare categorical variables. When continuous variables were converted to categorical variables, cut-off values were determined using receiver operating characteristic (ROC) curves. To identify predictors of adverse outcomes, forward stepwise multiple logistic regression analysis was used using variables of p b 0.05 in univariate analysis. A goodness-of-fit test used to assess the fit of logistic regression models was the Hosmer–Lemeshow test. In addition, we calculated sensitivities, specificities, positive predictive values, negative predictive values, positive likelihood ratios, and negative likelihood ratios for prediction of adverse outcomes. MedCalc, version 12.0 (MedCalc Software, Ostend, Belgium) was used for analysis of ROC curve. P-values b 0.05 were considered to indicate statistical significance.

A

B

Fig. 1. Measurement of right ventricle (RV)/left ventricle (LV) diameter ratio on computed tomography image. The RV (A) and LV (B) diameters were measured on the transverse section in which their diameters were greatest from the inner to the inner wall. Multiple pulmonary emboli (arrowheads) were noted at segmental pulmonary arteries.

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Table 1 Baseline and clinical characteristics (n = 657).

Age, years Female gender Body mass index, kg/m2 Unprovoked PE Risk factor for VTE Surgery or trauma Cancer Immobilization Previous VTE Comorbid condition Diabetes mellitus Chronic lung disease⁎ Cerebrovascular accident Ischemic heart disease Congestive heart failure Atrial fibrillation Chronic liver disease Chronic kidney disease Varicose vein Peripheral artery disease Connective tissue disease Systolic BP, mmHg Systolic BP b90 mmHg Heart rate,/min Tachycardia, heart rate N110/min PESI PESI class IV-V Thrombolytic therapy Length of hospital stay, days VTE recurrence In-hospital mortality

Table 3 Electrocardiographic, echocardiographic, and computed tomographic findings.

Adverse outcome (n = 69)

Low risk (n = 588)

p-value

69 (62–75) 52 (75.4) 23.5(21.1-25.6) 29 (42.0)

68 (57–75) 310 (52.7) 23.8(21.3-26.0) 178 (30.3)

0.041 b0.001 0.442 0.153

10 (14.5) 17 (24.6) 21 (30.4) 3 (4.3) 15 (21.7) 4 (5.8) 9 (13.0) 4 (5.8) 1 (1.4) 0 (0.0) 2 (2.9) 1 (1.4) 1 (1.4) 0 (0) 0 (0) 113 (93–140) 15 (21.7) 99 (82–113) 23 (33.3) 100 (72–120) 29 (42.6) 32 (46.4) 12 (7–18) 5 (7.2) 28 (40.6)

177 (30.1) 139 (23.6) 216 (36.7) 21 (3.6)

0.007 0.881 0.583 0.324

92 (15.6) 57 (9.7) 43 (7.3) 23 (3.9) 20 (3.4) 9 (1.5) 9 (1.5) 8 (1.4) 5 (0.9) 5 (0.9) 5 (0.9) 126 (114–140) 9 (1.5) 88 (76–101) 83 (14.1) 78 (65–96) 88 (15.1) 8 (1.4) 12 (8–19) 6 (1.0) 24 (4.1)

0.226 0.383 0.101 0.515 0.715 0.608 0.324 1.000 0.487 1.000 1.000 0.001 b0.001 0.007 b0.001 b0.001 b0.001 b0.001 0.436 0.003 b0.001

Data are presented as median (interquartile range) or n (%). PE, pulmonary embolism; VTE, venous thromboembolism; BP, blood pressure; PESI, pulmonary embolism severity index. *Chronic lung disease includes chronic obstructive pulmonary disease, asthma, bronchiectasis, idiopathic pulmonary fibrosis, pneumoconiosis, and tuberculosis-destroyed lung.

Results Clinical Characteristics Demographic and clinical characteristics are summarized in Table 1. The adverse outcome group comprised 69 patients (11%). The adverse outcome group contained more women than the low risk group (75% [52/69] versus 53% [310/588], p b 0.001), and median patient age in the adverse outcome group was greater (69 years [IQR, 62–75 years] versus 68 years [57–75 years], p = 0.041). Regarding risk factors of VTE, surgery or trauma was significantly less common in the adverse outcome group than in the low risk group (15% [n = 10] versus 30% [n = 177], p = 0.007). The frequencies of hypotension and tachycardia were significantly higher in the adverse outcome group (22% [n = 15] versus 2% [n = 9], p b 0.001; and 33% [n = 23] versus 14% [n = 83], p b 0.001, respectively). High PESI score (class IV-V) was more common in the adverse outcome group (43% [n = 29] versus 15% [n = 88],

n ECG change⁎ Echocardiography RV dysfunction RVSP, mmHg RVSP N40 mmHg Chest CT Central pulmonary arteries† RV/LV diameter ratio RV/LV diameter ratio ≥1

Adverse outcome

n

Low risk

p-value

69

33 (52.4)

588

97 (22.0)

b0.001

28 30 30

18 (64.3) 52 (40–72) 22 (73.3)

151 145 145

43 (28.5) 40 (29–59) 71 (49.0)

b0.001 b0.001 0.016

69

47 (68.1)

588

189 (32.5)

b0.001

69 1.24 (0.91-1.52) 588 0.88 (0.75-1.06) b0.001 69 47 (69.1) 588 187 (32.2) b0.001

Data are presented as median (interquartile range) or n (%). ECG, electrocardiogram; PE, pulmonary embolism; RV, right ventricle; RVSP, right ventricular systolic pressure. *ECG change includes T-wave inversion on precordial leads, Q1S3T3, and right bundle branch block. †Central pulmonary arteries mean right or left pulmonary artery or more proximal location.

p b 0.001). The median duration of follow-up was 357 days (IQR,125847 days). Laboratory and Imaging Studies Laboratory findings are presented in Table 2. The frequencies of high NT-proBNP (≥ 1,136 pg/ml) and troponin I elevation (≥ 0.05 ng/ml) were significantly higher in the adverse outcome group than in the low risk group (71% [30/42] versus 30% [14/350], p b 0.001; 72% [40/ 55] versus 35% [145/418], p b 0.001, respectively). Regarding ABGA data, PaO2/FiO2 and PaCO2 were significantly lower in the adverse outcome group than in the low risk group (278 mmHg [198–332 mmHg] versus 342 mmHg [274–393 mmHg], p b 0.001; and 28 mmHg [25– 32 mmHg] versus 31 mmHg [27–35 mmHg], p = 0.022, respectively). ECG changes suggestive of RV dysfunction, echocardiographic RV dysfunction, and pulmonary hypertension (RVSP N40 mmHg) were more frequently observed in the adverse outcome group than in the low risk group (52% [n = 33] versus 22% [n = 97], p b 0.001; 64% [18/28] versus 29% [43/151], p b 0.001; and 73% [22/30] versus 49% [71/145], p b 0.001, respectively) (Table 3). On CT images, central pulmonary arteries were more commonly involved by thromboemboli (68% [n = 47] versus 33% [n = 189], p b 0.001) and the prevalence of RVD-CT (RV/LV diameter ratio ≥ 1) were higher in the adverse outcome group (69% [n = 47] versus 32% [n = 187], p b 0.001, respectively). Predictors of Adverse Outcomes To identify predictors of adverse outcomes, we performed multiple logistic regression analysis. Of parameters that significantly differed in the univariate analysis, age, gender, hypotension, and tachycardia were excluded in the multivariate analysis, because these were a component of PESI score. ECG changes and involvement of central pulmonary arteries were also excluded in the multivariate

Table 2 Laboratory findings.

NT-proBNP, pg/ml NT-proBNP ≥1,136 pg/ml Troponin I, ng/ml Troponin I ≥0.05 ng/ml PaO2/FIO2 PaCO2, mmHg

n

Adverse outcome

n

Low risk

p-value

42 42 55 55 50 50

2,156 (643–4,914) 30 (71.4) 0.13 (0.05-0.37) 40 (72.2) 278 (198–332) 28 (25–32)

350 350 418 418 330 330

363 (103–1,545) 104 (29.7) 0.04 (0.04-0.09) 145 (34.7) 342 (274–393) 31 (27–35)

0.010 b0.001 0.039 b0.001 b0.001 0.022

Data are presented as median (interquartile range) or n (%). NT-proBNP, N-terminal-pro-B-type natriuretic peptide.

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Discussion

Table 4 Multivariate analysis for predictors of adverse clinical outcome. Predictors

Odds ratio

95% confidence interval

p-value

PESI⁎ NT-proBNP† Troponin I‡ RVD-CT§

6.26 4.71 2.71 3.00

2.74-14.31 2.00-11.07 1.15-6.39 1.27-7.07

b0.001 b0.001 0.023 0.012

PESI, pulmonary embolism severity index; NT-proBNP, N-terminal-pro-B-type natriuretic peptide; RV, right ventricle; RVD-CT, right ventricular dilation on computed tomography. *PESI, class IV-V; †NT-proBNP, ≥1,136 pg/ml; ‡troponin I, ≥0.05 ng/ml; §RVD-CT, right ventricle/left ventricle diameter ratio ≥1.

analysis because of significant correlations with other predictors (data not shown), and PaO2 /FIO2 , PaCO 2, and echocardiographic parameters because of substantial missing data. Consequently, surgery or trauma, PESI (class IV-V), NT-proBNP (≥ 1,136 pg/ml), troponin I (≥0.05 ng/ml), and RVD-CT were included in the multivariate analysis. The Hosmer–Lemeshow test indicated that the overall model fit was good (p = 0.789). It was found that PESI, NT-proBNP, troponin I, and RVD-CT significantly predicted adverse outcomes (odds ratio [OR] 6.26, 95% confidence interval [CI] 2.74-14.31, p b 0.001; OR 4.71, 95% CI 2.00-11.07, p b 0.001; OR 2.71, 95% CI 1.15-6.39, p = 0.023; and OR 3.00, 95% CI 1.27-7.07, p = 0.012, respectively) (Table 4). Of four categorical prognostic variables that predicted an adverse outcome, PESI had the highest positive predictive value (24.8%) and positive likelihood ratio (2.8) (Table 5). Of the PESI-based two-test combinations, the addition of NT-proBNP exhibited the highest positive predictive value (50.0%) and positive likelihood ratio (8.4), and this was followed by PESI/RVD-CT combination (43.1% and 6.5, respectively). Of the combinations of three predictors, PESI/NT-proBNP/troponin I had the highest positive predictive value (64.7%) and positive likelihood ratio (15.1), and this was followed by the PESI/NT-proBNP/RVD-CT combination (62.5% and 14.0, respectively). All combinations of three tests increased the positive likelihood ratio to greater than 10. Finally, a combination of all four predictors had the highest positive predictive value (71.4%) and positive likelihood ratio (20.8). RVD-CT enhanced the positive predictive values and positive likelihood ratios for adverse outcomes whenever RVD-CT was added to other prognostic markers or their combinations. C-statistics were calculated to examine whether the addition of RVD-CT to PESI, PESI/NT-proBNP, or PESI/NT-proBNP/troponin I combinations increased the predictive performance for an adverse outcome (Table 5). The RVD-CT/PESI combination exhibited significantly higher C-statistic, as compared with PESI alone (p = 0.009), and the RVD-CT/ PESI/NT-proBNP combination tended to have higher C-statistic than PESI/NT-proBNP (p = 0.056). However, the four-test combination did not significantly increase C-statistic as compared with PESI/NTproBNP/troponin I.

The present study indicated that RVD-CT is a significant prognostic factor of an adverse outcome for acute PE along with PESI score, NTproBNP, and troponin I. In addition, RVD-CT elevated prognostic values for an adverse outcome when used in combination with other prognostic markers. For a considerable time, echocardiography has been the most useful noninvasive method for detecting RV dysfunction in patients with acute PE [1,7,18]. However, echocardiography is not available at some institutions and commonly cannot image RV, particularly in patients with emphysema or obese patients when performed by a less experienced operator [24]. Furthermore, echocardiographic RV dysfunction has a low positive predictive value for PE-related in-hospital death [25,26]. In contrast, CT is currently the first imaging modality for PE and is easily accessible, and thus, many studies have addressed the prognostic role of RVD-CT. However, its role for predicting the mortality of PE remains controversial. The majority of positive results have been obtained in studies that used reconstructed CT images to get the image of fourchamber views [27,28]. Studies that adopted baseline CT images have produced mixed negative [15,20,29] and positive results [9,30]. A recent prospective multicenter study did not support the use of the presence or absence of RVD on MDCT images to drive decision-making regarding outpatient management or thrombolytic therapy for the treatment of acute PE [20]. However, the baseline CT images used in the present study showed that RVD-CT independently predicted adverse outcomes. Because a single prognostic factor is generally inadequate for predicting poor clinical outcome, the need for a combination of multiple prognostic variables is often emphasized [10]. Previously, a combination of CT parameters and troponin I or T was found to improve the prognostic value for adverse outcomes in PE [31,32]. RVD-CT has been reported to be a marker of poor outcomes, independently of PESI score [9], and in the present study, RVD-CT increased prognostic yield, when combined with already known prognostic factors of PE, such as PESI score alone, any combinations of two variables, or in combination with the other three variables. Negative predictive value for an adverse outcome can be used to identify low risk patients who may be candidates for treatment as outpatients or on a general ward. The combination of prognostic factors did not increase negative predictive values in the present study. In contrast, high positive predictive value for an adverse outcome can predicts patients with poor prognosis. The positive predictive values for an adverse outcome were increased in two-, three-, and four-test combinations of predictors. These results support the notion that a combination of multiple prognostic variables better supports predictions of adverse prognoses than a single predictor. On the other hand, the addition of RVD-CT to PESI alone or PESI/NT-proBNP significantly raised or tended to elevate C-statistic, but the four-test combination did not have significantly higher C-statistic as compared with PESI/NTproBNP/troponin I.

Table 5 Prognostic characteristics of the predictors for adverse clinical outcomes. Predictors⁎

Sensitivity (%)

Specificity (%)

PPV (%)

NPV (%)

PLR

NLR

C-statistic

p-value

PESI⁎ NT-proBNP† Troponin I‡ RVD-CT§ PESI⁎ + NT-proBNP† PESI⁎ + troponin I‡ PESI⁎ + RVD-CT§ PESI⁎ + NT-proBNP† + troponin I‡ PESI⁎ + NT-proBNP† + RVD-CT§ PESI⁎ + troponin I‡ + RVD-CT§ PESI⁎ + NT-proBNP† + troponin I‡ + RVD-CT§

42.7 70.4 72.7 69.1 29.3 37.0 32.4 27.5 24.4 31.5 25.0

84.9 70.3 65.3 67.8 96.5 93.2 95.0 98.2 98.3 97.3 98.8

24.8 22.4 21.6 20.1 50.0 41.7 43.1 64.7 62.5 60.7 71.4

92.7 95.4 94.9 94.9 92.0 91.9 92.3 91.8 91.6 91.5 91.5

2.8 2.4 2.1 2.1 8.4 5.5 6.5 15.1 14.0 11.8 20.8

0.7 0.4 0.4 0.5 0.7 0.7 0.7 0.7 0.8 0.7 0.8

0.648 0.710 0.702 0.686 0.784 0.760 0.754 0.814 0.818 0.786 0.835

0.050 0.043 0.042 0.042 0.037 0.042 0.041 0.033 0.033 0.036 0.030

PPV, positive predictive value; NPV, negative predictive value; PLR, positive likelihood ratio; NLR, negative likelihood ratio; PESI, pulmonary embolism severity index; NT-proBNP, Nterminal-pro-B-type natriuretic peptide; RVD-CT, right ventricular dilation on computed tomography. *PESI, class IV-V; †NT-proBNP, ≥1,136 pg/ml; ‡troponin I, ≥0.05 ng/ml; §RVDCT, right ventricle/left ventricle diameter ratio ≥1.

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The present study has several limitations. First, due to retrospective nature of this study, confounding by indication should be noted, although previously established risk factors for poor prognosis were assessed [10]. In particular, because missing values of laboratory and echocardiographic measurements were substantial, these could have affected our results. Second, the potential impact of PE-specific therapy on clinical outcome was not considered. Third, RV and LV diameters were measured using baseline axial CT views rather than ECG-gated reconstructed four-chamber CT views. Reconstructed CT views have been shown to be more accurate for determining RV and LV diameters but are impractical and time-consuming [33]. In conclusion, the study indicates that RVD-CT is an independent prognostic factor of adverse clinical outcomes in patients with PE. Furthermore, RVD-CT was found to provide an additional diagnostic benefit when combined with the established prognostic factors, including PESI, NT-proBNP, and troponin I.

Conflict of Interest Statement None of the authors has a financial relationship with a commercial entity that has an interest in the subject of this manuscript.

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