Radiology
Thoracic Imaging Andrew S. Wu, BA John A. Pezzullo, MD John J. Cronan, MD David D. Hou, MD William W. Mayo-Smith, MD
Index terms: Embolism, pulmonary, 60.72 Pulmonary arteries, CT, 564.12113, 564.12116, 944.12916 Published online before print 10.1148/radiol.2303030083 Radiology 2004; 230:831– 835 Abbreviation: PE ⫽ pulmonary embolus 1
From the Department of Diagnostic Imaging, Rhode Island Hospital, Brown Medical School, 593 Eddy St, Main 3, Providence, RI 02903. From the 2002 RSNA scientific assembly. Received January 18, 2003; revision requested March 26; final revision received August 2; accepted September 29. Address correspondence to J.A.P. (e-mail:
[email protected]).
CT Pulmonary Angiography: Quantification of Pulmonary Embolus as a Predictor of Patient Outcome—Initial Experience1 PURPOSE: To determine whether quantification of pulmonary embolus (PE) with computed tomographic (CT) pulmonary angiography by using a standardized index is a predictor of patient outcome. MATERIALS AND METHODS: Multi– detector row CT was performed in 59 hospitalized patients (mean age, 61 years; age range, 22– 89 years). PE was identified retrospectively by two radiologists who were blinded to patient outcome. A pulmonary arterial obstruction index was derived for each set of images on the basis of embolus size and location. By using logistic regression, PE indexes were compared with patient outcome—survival or death—to determine if there was a correlation between PE volume and survival. RESULTS: The PE index is a significant predictor of patient outcome (P ⫽ .002). One of 53 patients (1.9%) with an index of less than 60% died. Cause of death was end-stage malignancy. Five of six patients (83%) with an index of 60% and higher died. All five deaths were related to the presence of PE. The one survivor with a PE index higher than 60% received thrombolytic therapy. By using a cutoff of 60%, the PE index was used to identify 52 of 53 (98%) patients who survived and five of six (83%) patients who died. CONCLUSION: Preliminary evidence suggests that quantification of clot with CT pulmonary angiography is an important predictor of patient death in the setting of PE. ©
Author contributions: Guarantor of integrity of entire study, A.S.W.; study concepts and design, all authors; literature research, J.J.C., J.A.P., A.S.W.; clinical studies, J.J.C., J.A.P.; data acquisition and analysis/ interpretation, all authors; statistical analysis, A.S.W.; manuscript preparation, definition of intellectual content, editing, revision/review, and final version approval, all authors ©
RSNA, 2004
RSNA, 2004
Computed tomographic (CT) pulmonary angiography is gaining wide acceptance as a first-line examination for the detection of pulmonary emboli (PE) (1). With the development of narrow collimation, multi– detector row CT, and more powerful workstations for analysis and review, CT pulmonary angiography has become more accurate (2,3) in the detection of PE and more widely used (1) in diagnosis. Some studies have shown that CT pulmonary angiography is more cost-effective than conventional angiography in the work-up of patients suspected of having PE (4,5). Investigators in other studies (6,7), including a recent meta-analysis (8), have recommended using CT pulmonary angiography as the modality of choice in the assessment of patients suspected of having PE. Despite the new advances in and the acceptance of CT pulmonary angiography as a standard diagnostic technique for assessment of patients suspected of having PE, current classification of CT pulmonary angiography results remains either positive or negative, with an occasional report noting the massive nature of PE (9). Miller et al (10) derived an index for the quantification of clot burden for conventional angiography, and more recently, Qanadli et al (11) described an index for CT pulmonary angiography. To our knowledge, no attempt has been made to relate the amount of PE to the clinical outcome, and little consideration has been given to the implications of clot load on therapy. 831
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The objective of this study was to determine whether quantification of PE with CT pulmonary angiography by using a standardized index (11) is a predictor of patient outcome.
MATERIALS AND METHODS Study Population This study was approved by the institutional review board; informed consent was not required. We retrospectively identified all CT pulmonary angiography procedures performed at our institution between January 24, 2001, and January 23, 2002 (n ⫽ 462). CT records were identified through the diagnostic imaging database. The CT report for each study was reviewed from the database by one author (A.S.W.), and positive studies were selected (81 positive studies in 77 patients). Magnetic optical disk archives (Sony Electronics, Park Ridge, NJ) of the studies were retrieved by technologists. Medical records of patients who underwent the examinations were reviewed by two authors (A.S.W., D.D.H.). Fifteen examinations were excluded from this study: seven because the examination results could not be located in the CT archive, five because the patient chart could not be located, and three because of poor image quality. In the opinion of the two reviewing radiologists, poor image quality provided inadequate information due to artifacts, suboptimal contrast material delivery, other technical difficulties, or a combination of these factors. Six studies that were initially considered positive for PE were considered negative at subsequent rereview and were excluded from the study. Sixty studies in 59 patients remained. Mean patient age was 61 years (age range, 22– 89 years). There were 37 women (mean age, 61 years; age range, 22– 89 years) and 22 men (mean age, 62 years; age range, 31– 83 years) in the study, and there was no statistically significant difference in the age distribution between the sexes (P ⫽ .94). In one patient who underwent two CT examinations, the images from the most recent examination were used for analysis—thus, 59 imaging studies in 59 patients.
CT Imaging All CT scans were obtained by using a multi– detector row CT scanner (GE Lightspeed QXi; GE Medical Systems, Milwaukee, Wis) with the following parameters: 1.25-mm collimation; 7.5 mm/sec table speed, and 15-cm z-axis coverage. Images 832
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Figure 1. Diagram of the pulmonary arterial tree, including the 10 segmental branches for each lung: three to the upper lobes, two to the middle lobe and lingula, and five to each lower lobe. The segmental arteries are the basic unit of scoring in the PE index. LPA ⫽ left pulmonary artery, RPA ⫽ right pulmonary artery.
were acquired in the caudocranial direction from the costophrenic angle to 3 cm above the aortic arch in one breath hold. A total of 130 mL of low-osmolar contrast material was injected at a rate of 4 mL/ sec, and a scan delay of 16 seconds was used in most patients. For patients with presumed cardiac output abnormalities (as determined by means of chart review before CT examination), a timing bolus was used to optimize pulmonary artery opacification.
Image Interpretation Images from each CT examination were loaded into a workstation (Sparc; Sun Microsystems, Santa Clara, Calif) and reviewed together by two radiologists (J.J.C., J.A.P.) with 6 years of combined experience in interpretation of CT pulmonary angiographic images. Images were viewed on the workstation by using standard mediastinal windows with realtime ability to change the window and level settings for optimal vessel visualization. The two radiologists were blinded to the clinical outcome of the patients. Images were interpreted by means of consensus. The helical CT criterion used to diagnose pulmonary emboli consisted of direct visualization of endoluminal thrombus. A thrombus was considered nonocclusive if contrast material was seen in the vessel adjacent to the filling defect. A thrombus
was considered completely occlusive if there was (a) complete endoluminal filling of the vessel with thrombus, (b) nonperfusion of the distal vessel, or (c) attenuation of distal segmental and subsegmental branches in the occluded vascular territory, which resulted in a hyperlucent lung. Pertinent data collected for this study included (a) location and number of filling defects and (b) occlusive versus nonocclusive nature of the filling defect. The locations of filling detects were marked on a diagram of the pulmonary arterial vasculature, with each lung regarded as having 10 segmental arteries, as shown in Figure 1. A PE index was derived from the amount and location of the thrombus on CT images on the basis of a study by Qanadli et al (11). The index is defined as the product of N ⫻ 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, defined as 1 for partial obstruction and 2 for total obstruction. The fraction of vessel lumen occupied by the embolus— embolus width divided by vessel lumen diameter—was not graded. A thrombus either partially occluded the vessel (D ⫽ 1, occupying more than 0% and less than 100% of vessel space) or completely occluded the vessel (D ⫽ 2, occupying 100% of vessel space). Each Wu et al
TABLE 1 Characteristics of 59 Patients with PE
Radiology
A: Basic Characteristics No. of Patients
Characteristic Patient sex Female Male Patient outcome Survival Death Preexisting cardiac condition* Presence of cancer Hypercoagulable state
37 (63) 22 (37) 53 (90) 6 (10) 18 (30) 17 (29) 2 (3)
B: Additional Characteristics Characteristic
Mean ⫾ SD
Median
Patient age (y) PE index (%)
61 ⫾ 18.4 22 ⫾ 23.2
66 10
Note.—Numbers in parentheses are percentages. * Including cardiomyopathy, infarct, pulmonary arterial hypertension, conduction abnormality, and congenital anomaly.
Figure 2. Histogram shows the distribution of clot burden as measured with the CT PE index. Each bar shows the number of patients with a range of indexes as indicated below the bar. For example, the bar above “40ⱕX⬍50” shows that two patients had indexes greater than or equal to 40% and less than 50%. Most patients received an index of less than 30%.
Chart Review TABLE 2 Logistic Regression Models for PE Index as a Predictor of Patient Outcome Model
Odds Ratio*
95% CI
P Value
1, unadjusted† 2, adjusted‡
2.11 2.32
1.31, 3.39 1.28, 4.18
.002 .005
* For increments of 10% in PE index. † Independent variable, PE index only. ‡ Independent variables: PE index, age, sex, presence of cancer, preexisting cardiac conditions, and other documented hypercoagulable states.
detected clot had N and D values assigned to it. For example, the presence of embolus in a segmental artery was scored 1 point. This value was multiplied by a factor D, defined as 1 for a partially occlusive embolus and 2 for a completely occlusive embolus. Thus, a totally occlusive thrombus in a segmental artery was assigned a value of 2. A clot in a proximal artery that gives rise to segmental arteries was scored as though each segmental artery had an embolus with the same degree of obstruction as the proximal embolus. Subsegmental emboli were scored as a partial obstruction of the segmental artery. Accordingly, the maximum obstruction score for each patient was 40 (20 for each lung), and this score was converted into a percentage. Volume 230
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For each patient, the following information was collected: (a) patient outcome—survival or death—and cause and time of death as noted on the death certificate, which were determined at chart review; if the patient survived, time of discharge was noted; (b) anticoagulation therapy received (yes or no); (c) thrombolytic therapy received (yes or no); (d) preexisting cardiac conditions, defined as any combination of the following: cardiomyopathy, infarct, pulmonary arterial hypertension, conduction abnormalities, and congenital anomaly; and (e) risk factors for deep venous thrombosis—that is, presence of cancer or other acquired or inherited hypercoagulable states.
Statistical Analysis Descriptive statistics were calculated for patient age and sex, PE index, survival, documented hypercoagulable state, and presence of cancer. Patient mortality rates were calculated on the basis of the PE index. Logistic regression analyses were performed to determine whether the PE index was a significant predictor of patient outcome. The outcome (dependent variable) was either survival (represented as 0) or death (represented as 1). Two models were constructed by using the PE index as a predictor. In the first model, the index was the sole independent variable, and a crude odds ratio was obtained. In the second model, we ad-
justed for patient age and sex, presence of cancer, preexisting cardiac conditions, and other documented hypercoagulable states. Odds ratios were obtained in terms of 10% increases in PE index versus survival. All analyses were performed by one author (A.S.W.) by using a software program (SPSS for Windows, version 10.0.1; SPSS, Chicago, Ill).
RESULTS Our results are summarized in Tables 1 and 2 and Figures 2 and 3. Patient characteristics, including age and mean PE index, are summarized in Table 1. Distribution of the clot burden as derived from the index is shown in Figure 2. All patients in the study population received anticoagulation therapy. Three patients (5.1%) received thrombolysis. Of all 59 patients, 53 (90%) survived and six (10%) died. Average time of death was approximately 6 days after CT pulmonary angiography (minimum, 0 days; maximum, 20 days; median, 1.5 days). The average follow-up for patients who survived was 12 days (minimum, 0 days; maximum, 77 days; median, 9 days). One of 53 (1.9%) patients with a PE index of less than 60% died. Five of six (83%) patients with a PE index of 60% and higher died. Figure 3 shows the distribution of PE index versus survival. There is a visually appreciable cutoff at the 60% index level that separates survival and death. CT Quantification of Pulmonary Embolus
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The patient who survived with an index of higher than 60% was one of two patients in this index category who received thrombolytic therapy. The other patient, who underwent thrombolysis, had an index of 92.5% and did not survive. All five deaths in the 60% and higher category were related to the presence of PE. In the group of patients with an index of less than 60%, the patient who died had Burkitt lymphoma with a high tumor burden and died of causes related to malignancy. Figure 4 is an example of two patients in the study with different PE indexes. The patient in Figure 4, A, was a 74-yearold man who had an isolated subsegmental clot (score of 1/40, or 2.5% PE index) and survived. The patient in Figure 4, B, was an 84-year-old woman who had a PE index of 75% (score of 30/40) and died of PE during her hospital stay. Logistic regression models demonstrated that the PE index is a significant predictor of patient death. In the first model, the index was the only independent variable, and outcome (survival or death) was the dependent variable. This model showed that the chances of death increased with increasing PE index (P ⫽ .002; odds ratio, 2.11 for a 10% increase in obstruction; 95% CI: 1.31, 3.39). The second model showed that the index remains a significant predictor of patient death after adjusting for patient age and sex, presence of cancer, preexisting cardiac conditions, and documented hypercoagulable state (P ⫽ .005; odds ratio, 2.32 for a 10% increase in obstruction; 95% CI: 1.28, 4.18) (Table 2).
DISCUSSION Most of the recent radiologic literature has focused on the accuracy of CT pulmonary angiography in the diagnosis of acute PE and has compared it with more conventional tests, including conventional angiography and ventilationperfusion nuclear medicine scanning (12–17). Despite recent advances, CT pulmonary angiography findings are typically reported dichotomously as either positive or negative, with little or no mention made of the amount of thrombus present. One would assume that the patient with a single isolated subsegmental embolus would have a different prognosis than a patient with a saddle embolus. Only recently have attempts been made to quantify the clot burden on the basis of CT angiographic findings (11). The development 834
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Figure 3. Graph shows clot burden, as quantified with the CT PE index, versus patient survival. Each diamond represents a patient. In the group with an index of less than 60%, one of 53 patients (1.9%) died (of cancer, not of PE). In the group with an index of 60% and higher, five of six (83%) patients died. The patient who survived in this group underwent thrombolytic therapy.
Figure 4. Transverse contrast material– enhanced CT images in two patients. Arrows indicate clot locations. A, Patient had a small subsegmental clot, received a PE index of 2.5%, and survived. B, Patient had multiple large emboli, received a PE index of 75%, and died of causes related to PE while hospitalized.
of such a clot burden index may have important prognostic and therapeutic implications and may provide a reproducible standard for measuring response to thrombolytic therapy. In this study, we have applied the CT PE index to predict patient outcome. To our knowledge, this is the first study performed to relate such an index to clinical outcome. The pulmonary arterial obstruction index used in this study is based on the description by Qanadli et al (11), where the segmental pulmonary arteries are the basic units for scoring, and a weighted factor is considered for occlusive versus
nonocclusive emboli. We report a mean percentage of pulmonary arterial obstruction of 22% (range, 2.5%–92.5%), which is slightly lower than the figure described by Qanadli et al (29%). The differences may be explained by the CT scanners used in the two studies—Qanadli et al used a double detector array with 5-mm collimation, while our examinations were performed with a four– detector row CT scanner with 1.25-mm collimation; we may have been able to detect more cases of small subsegmental emboli, which lowered our average PE index percentage. Another reason may be a lower threshold for ordering CT pulmoWu et al
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nary angiography examinations at our institution. Our preliminary findings suggest that the PE index may have important prognostic value, since patients with a pulmonary vascular obstruction of more than 60% tended to have a poor clinical outcome. In fact, 83% of the patients in our cohort with a PE index of higher than 60% died, while 52 of 53 (98%) patients with an index of less than 60% lived. This finding, if valid, would allow the stratification of a patient’s risk of death and might help identify patients who would benefit from more aggressive treatment strategies, such as thrombolysis. A stratification scheme is important for treatment with thrombolysis, since the risk of hemorrhage is approximately 12%, with little difference among thrombolytic agents (18). The overall mortality associated with thrombolytic hemorrhage is 1%–2% (19,20). This point underscores the need for a reproducible means to identify patients in whom the use of thrombolytics outweighs the risks of such therapy. Several limitations of this study should be addressed. First, with 1 year of CT angiography data, the number of available positive PE studies and, especially, the number of patients with massive PE were limited to 59 and six, respectively. More patients would provide more power for the study and allow more variables to be analyzed with precision. Second, nearly half of patients (26 of 59, or 44%) received a PE index of less than 10%, which raises the question of false-positive findings. Independent interpretation, interobserver data, and rereview of a representative portion of negative studies would have improved this aspect of the study. False-positive findings, however, do not diminish the data that show the impact of large PE on patient outcome. In this study, we sought to determine
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the predictive value of quantified CT pulmonary angiographic clot burden on the clinical outcome of patients with PE, and we found that the PE index is a significant predictor of patient mortality. Further studies on larger scales are needed to confirm the predictive value of the index, and prospective studies will be necessary to build and refine the index criteria, since it relates to thrombolytic therapy and patient risks. References 1. Costello P, Gupta KB. CT angiography gains acceptance in diagnosis of pulmonary emboli. Diagn Imaging (San Franc) 2000; 22:43– 45, 49, 87. 2. Raptopoulos V, Boiselle PM. Multi– detector row spiral CT pulmonary angiography: comparison with single– detector row spiral CT. Radiology 2001; 221:606 – 613. 3. Qanadli SD, Hajjam ME, Mesurolle B, et al. Pulmonary embolism detection: prospective evaluation of dual-section helical CT versus selective pulmonary arteriography in 157 patients. Radiology 2000; 217: 447– 455. 4. van Erkel AR, van Rossum AB, Bloem JL, Kievit J, Pattynama PM. Spiral CT angiography for suspected pulmonary embolism: a cost-effectiveness analysis. Radiology 1996; 201:29 –36. 5. Rosen MP. Spiral CT angiography for suspected pulmonary embolism: a cost-effectiveness analysis. Acad Radiol 1999; 6:72– 75. 6. McEwan L, Gandhi M, Andersen J, Manthey K. Can CT pulmonary angiography replace ventilation-perfusion scans as a first line investigation for pulmonary emboli? Australas Radiol 1999; 43:311–314. 7. Blachere H, Latrabe V, Montaudon M, et al. Pulmonary embolism revealed on helical CT angiography: comparison with ventilation-perfusion radionuclide lung scanning. AJR Am J Roentgenol 2000; 174:1041–1047. 8. Safriel Y, Zinn H. CT pulmonary angiography in the detection of pulmonary emboli: a meta-analysis of sensitivities and specificities. Clin Imaging 2002; 26:101– 105. 9. Oliver TB, Reid JH, Murchison JT. Interventricular septal shift due to massive pulmonary embolism shown by CT pul-
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