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Meta-Analysis: Outcomes in Patients with Suspected Pulmonary Embolism Managed with Computed Tomographic Pulmonary Angiography FREE

Lisa K. Moores, MD; William L. Jackson Jr., MD; Andrew F. Shorr, MD, MPH; and Jeffrey L. Jackson, MD, MPH
[+] Article and Author Information

From Walter Reed Army Medical Center, Washington, DC, and the Uniformed Services University of the Health Sciences, Bethesda, Maryland.


Disclaimer: The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the U.S. Department of the Army or the U.S. Department of Defense.

Acknowledgments: The authors thank Christopher Bennett, MD, for his expertise with CTPA and Mr. Robert J. Mohrman for his assistance with the literature search.

Potential Financial Conflicts of Interest: None disclosed.

Requests for Single Reprints: Lisa K. Moores, MD, Uniformed Services University of the Health Sciences, Walter Reed Army Medical Center, 6900 Georgia Avenue NW, Washington, DC 20307; e-mail, Lisa.Moores@na.amedd.army.mil.

Current Author Addresses: Drs. Moores, W.L. Jackson, and Schorr: Uniformed Services University of the Health Sciences, Walter Reed Army Medical Center, 6900 Georgia Avenue NW, Washington, DC 20307.

Dr. J.L. Jackson: Uniformed Services University, 4301 Jones Bridge Road, Bethesda, MD 20814.


Ann Intern Med. 2004;141(11):866-874. doi:10.7326/0003-4819-141-11-200412070-00011
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Background: Spiral computed tomographic pulmonary angiography (CTPA) is increasingly being used in the evaluation of patients with clinically suspected pulmonary embolism (PE). However, CTPA as a definitive diagnostic test may be limited by inadequate sensitivity, especially in instances of isolated subsegmental emboli.

Purpose: To assess the safety of withholding anticoagulation in patients with suspected PE and negative results on CTPA.

Data Sources: All relevant studies identified in MEDLINE (1966 to March 2004) and EMBASE (1974 to 2004) and in bibliographies of key articles. The search was not limited to the English language.

Study Selection: The authors selected all published studies that used CTPA to evaluate suspected PE and reported at least 3 months of follow-up in patients not receiving anticoagulation on the basis of a negative CTPA result.

Data Extraction: Two reviewers independently rated study quality on the basis of predetermined criteria. Data were extracted on participants, CTPA technique, diagnostic studies performed, prevalence of PE, number of patients with negative or indeterminate CTPA results who were followed, and subsequent rates of venous thromboembolism and fatal PE.

Data Synthesis: Twenty-three studies reported on 4657 patients with negative CTPA results who did not receive anticoagulation. The 3-month rate of subsequent venous thromboembolic events was 1.4% (95% CI, 1.1% to 1.8%), and the 3-month rate of fatal PE was 0.51% (CI, 0.33% to 0.76%).

Limitations: The CTPA technology used varied across studies and was not applied uniformly in the same step of diagnostic algorithms. Only 1 study used CTPA as the sole diagnostic test.

Conclusion: The rate of subsequent venous thromboembolism after negative results on CTPA is similar to that seen after negative results on conventional pulmonary angiography. It appears to be safe to withhold anticoagulation after negative CTPA results.

Editors' Notes
Context

Is it safe to withhold anticoagulation in adults with suspected pulmonary embolism (PE) and negative results on spiral computed tomographic pulmonary angiography (CTPA)?

Contribution

This meta-analysis summarized data from 23 studies that reported rates of thromboembolism among patients with suspected PE who did not receive anticoagulation after negative results on CTPA. Among 4657 patients, the 3-month risks for a thromboembolic event and fatal PE were 1.4% and 0.51%, respectively.

Cautions

Studies used early-generation CT technology and different diagnostic algorithms for thromboembolism.

Implications

Withholding anticoagulation from patients with low to moderate probability of PE and negative results on CTPA appears reasonable.

–The Editors

Pulmonary embolism (PE) remains a major cause of morbidity and mortality (1). The limitations of clinical examination in establishing a diagnosis of PE, as well as the perils of unnecessary anticoagulation and untreated clots, mandate use of judicious objective diagnostic testing in the evaluation of this disorder. Spiral computed tomographic pulmonary angiography (CTPA) has become an integral part of the diagnostic evaluation for suspected PE, given its widespread availability, ease of acquisition, favorable performance characteristics (2), and utility in revealing alternative diagnoses (34). Researchers have been cautiously optimistic that CTPA may be useful as a definitive study to exclude PE (5).

However, CTPA is often applied as part of an algorithmic screening approach that includes other diagnostic tests, including pretest prediction models, d-dimer testing, lower-extremity compression ultrasonography, and lung scintigraphy (3, 613). Many of these algorithms recommend conventional pulmonary angiography (CPA) as the gold standard (14). Although screening algorithms are reported to have good efficacy, they remain cumbersome to apply (15) and may be considerably underused in clinical practice (16). Some recent investigations suggest that CTPA merits consideration as a definitive diagnostic study (1719). However, many authors remain unconvinced that negative CTPA results alone can reliably exclude clinically significant pulmonary emboli (2021).

Bates and Ginsberg (20) have proposed that acceptance of CTPA as a definitive study would require establishment of its interobserver and intraobserver variability and study characteristics, determination of its accuracy, and an assessment of outcomes after anticoagulation is withheld because of a negative test result. The first 2 criteria have been evaluated (2122). In the current study, we performed a systematic review of the literature and conducted a meta-analysis of eligible studies to determine the safety and efficacy of withholding systemic anticoagulation after negative results on CTPA for PE.

We searched MEDLINE (1966 to March 2004) and EMBASE (1974 to 2004) using the terms pulmonary embolism, computed x-ray tomography, CTPA, angiography, sensitivity and specificity, prognosis, and recurrence. We augmented our search by reviewing the reference lists of retrieved articles and review articles, our personal files, and reference lists of related articles in our files. Our medical librarian performed an independent search to ensure completeness. The search was not limited to the English language, but only published reports were included (Figure 1).

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Figure 1.
Flow diagram of study selection.

CTPA = computed tomographic pulmonary angiography; PE = pulmonary embolism.

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Study Identification and Eligibility

We attempted to identify all published studies that examined the rate of subsequent symptomatic venous thromboembolism (VTE) in patients who did not receive anticoagulation after negative or indeterminate CTPA results. To be included in the analysis, studies had to 1) have a consecutive sample or a well-defined reason for a selected sample (for example, inclusion of only patients with underlying cardiopulmonary disease or those referred to specialty centers); 2) define the diagnostic strategy used to confirm or exclude VTE; 3) withhold anticoagulation or clearly state the reason for administering anticoagulation when VTE was excluded (patients who received anticoagulation were excluded from the final analysis); 4) have a minimum of 3 months of follow-up; and 5) report subsequent symptomatic VTE events and the means of confirmation.

Study Quality

Two reviewers independently rated each study's quality. Because there are no validated tools for quality assessment of outcome studies, we adapted the McMaster criteria for evaluating the validity of studies about prognosis (23). Studies were assessed for presence of 9 features: description of patient sample characteristics, description of inclusion and exclusion criteria, potential selection bias, length of follow-up, completeness of follow-up, description of patients lost to follow-up, description of reasons for incomplete follow-up, definition of outcomes at the start of the study, and objectivity of outcomes. The intraclass correlation coefficient for agreement between the 2 raters on overall quality rating for all included studies was 0.85 (P < 0.001). Disagreements were resolved by consensus. In addition to abstracted data on patients, CTPA performance, and outcomes, we recorded the number of patients who had initial nondiagnostic CTPA results and follow-up of these patients if reported. Patients who received anticoagulation despite initial negative results on CTPA were excluded from the final analysis. Although some studies included a longer follow-up period, we limited our analysis to the first 3 months after negative results on CTPA because events after 3 months are likely to be new rather than recurrences.

Statistical Analysis

The rates of subsequent VTE events and fatal PE were calculated from the abstracted numbers for each study. Extracted outcomes were the proportion of individuals with negative results on CTPA who subsequently experienced pulmonary emboli, fatal or otherwise. These data were combined by using an approximation to the inverse variance approach, effectively weighting each study according to its sample size (24). The 95% CI for each study and for the overall effect was calculated by using exact binomial methods. Heterogeneity was assessed visually with Galbraith plots (25). Publication bias was assessed visually by using funnel plots and by statistically using the method of Egger and colleagues (26). The sensitivity of our results to potential publication bias was assessed by using the methods of Duval and Tweedie (27). We performed sensitivity analyses, assessing the effects of type of study (prospective vs. retrospective), year of study, whether patients were consecutive or selected, generation of computed tomography (CT) scanner, the thickness of CT cuts, caudocranial image acquisition, view box interpretation, and the prevalence of PE.

Role of the Funding Source

No funding was received in support of this review.

We identified 640 abstracts in our search. Most were excluded because they did not include outcome data on patients not treated with anticoagulants (Figure 1). Among the 27 remaining articles, 4 were excluded: 3 had insufficient follow-up data (4, 2829) and 1 reported duplicate data (30) that were presented as part of the final report of a prospective study (31). Therefore, 23 articles were included in our analysis (3, 6, 1113, 15, 1719, 3144). One of these (33) included 35 patients from another study (32).

Qualitative Review

The 23 studies included 15 prospective and 8 retrospective trials (Table). Study samples ranged from 54 to 1512, averaging 403 patients. Seventeen of the included studies examined consecutive patients, and 6 included selected patient samples. Overall, the mean prevalence of PE was 19.8% (range, 13% to 42%). Three studies (34, 3738) enrolled only patients in whom PE had been excluded and therefore did not report on prevalence in the sample. Nine of the studies included images obtained in the caudocranial direction, and 15 interpreted images on view box stations. The average CT scanner thickness was 2.1 mm (range, 2 to 5 mm). Ten prospective studies used CTPA with other diagnostic methods as part of a predetermined algorithm (3, 6, 1113, 3133, 35, 40). Pretest probability was used in 6 studies (6, 1213, 3132, 35), lung scintigraphy in 5 (1112, 3132, 35), lower-extremity compression ultrasonography in 6 (3, 13, 3133, 40), and d-dimer testing in 4 (6, 11, 33, 40). Fourteen studies (3, 1213, 15, 1719, 31, 33, 3637, 39, 41, 43) used objective imaging to confirm subsequent VTE events, while only 6 (3, 13, 15, 18, 34, 39) used autopsy confirmation or central adjudication to confirm fatal events.

Table Jump PlaceholderTable.  Data Extracted from Individual Studies

Twenty-one of the studies included a small proportion of patients (n = 492) who received anticoagulation despite negative results on CTPA. The reasons for anticoagulation included presence of deep venous thrombosis on concomitant ultrasonography (n = 70), chronic VTE (n = 68), and cardiac arrhythmias or other cardiac abnormalities (n = 204). Four patients had positive results on another test (ventilation–perfusion scanning or CPA) that suggested PE, while 65 patients (13%) were listed as having nonthromboembolic disorders. The reason for anticoagulation was not stated in 63 patients. Only 18 patients received anticoagulation because of persistent high clinical suspicion of PE despite negative results on CTPA. These patients were not included in our analysis of outcomes.

Overall quality ratings ranged from 3 to 9 (Appendix Table). Common quality problems included inadequately clear inclusion and exclusion criteria in 6 studies, potential selection bias in 16 studies, incomplete follow-up in 13 studies, inadequate description of the patients lost to follow-up in 14 studies, inadequate description of the reason for incomplete follow-up in 7 studies, and problems with the objectivity of outcome assessment in 9 studies.

Table Jump PlaceholderAppendix Table.  Quality Ratings of Included Studies

Three studies (3, 6, 12) met all 9 criteria assessing methodologic quality. In an observational study, Perrier and colleagues (6) performed CTPA in 299 consecutive outpatients who had suspected PE and plasma d-dimer levels greater than 500 µg/L; PE was diagnosed by using a previously validated strategy (10) that did not include CTPA results. Thirty-four patients with negative CTPA results initially received a diagnosis of PE by ventilation–perfusion scanning, lower-extremity compression ultrasonography, or CPA; these patients received anticoagulation. At 3-month follow-up, none of the 157 patients who did not have PE on CTPA and did not receive anticoagulation had experienced recurrent or fatal PE. Of note, despite its strengths, this study was not included in our pooled event rate because CTPA results did not influence patient management and subsequent VTE events could not be assigned to CTPA results.

Ost and colleagues (12) performed CTPA in 103 patients with high pretest clinical suspicion for PE and nondiagnostic results on ventilation–perfusion scanning. Three of 71 patients with negative CTPA results subsequently developed nonfatal VTE at 6-month follow-up, with a negative predictive value of 96% when clinical outcome was used as the reference standard. Van Strijen and associates (3) studied 510 consecutive patients with suspected PE by using sequential single-detector CTPA and lower-extremity compression ultrasonography. Two of 248 patients with negative results on CTPA and no alternative diagnosis had positive results on lower-extremity compression ultrasonography. Of the 376 patients who had negative results on diagnostic studies and did not receive anticoagulation, 3 subsequently developed VTE during 3-month follow-up (VTE rate, 0.8% [CI, 0.2% to 2.3%]).

Quantitative Review

When all extracted data were pooled, 4657 patients were eligible for analysis. The rate of subsequent VTE (both nonfatal and fatal) among these studies ranged from 0% to 4.9%, with no evidence of heterogeneity. Over all studies, the pooled rate of VTE during 3-month follow-up among patients with negative CTPA results was 1.4% (CI, 1.1% to 1.8%) (Figure 2, top). Fatal PE occurred in 24 patients (pooled risk, 0.51% [CI, 0.33% to 0.76%]) (Figure 2, bottom).

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Figure 2.
Forest plots of total venous thromboembolism (VTE) events (top) and fatal pulmonary embolism (PE) events (bottom).

The number of patients for each study is the number of patients eligible for outcome assessment, and the event rates are a combination of recurrent VTE and fatal PE (see Table). Values in parentheses on the right-hand side of the figure are the upper bound of the CI unless otherwise indicated.

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Among the 15 prospective studies, 2361 patients were eligible for analysis. Subsequent VTE events occurred in 39 patients (pooled risk, 1.2% [CI, 0.6% to 1.8]), and fatal PE occurred in 15, yielding a pooled rate of 0.26% (CI, −0.5% to 52.5%). Of the 9 studies that followed patients for longer than 3 months, 8 studies, 5 of them prospective, recorded at least a mean of 6 months of follow-up. Only 1 subsequent PE was documented beyond the 3-month follow-up period (44).

Sensitivity Analysis

Our reported study outcomes for both total VTE and fatal PE rates were not affected by year of study, study type (prospective vs. retrospective), patient sample (consecutive vs. selected), the generation of the scanner, the thickness of scanner cuts, caudocranial image acquisition, image reading (view box vs. no view box), performance of other studies as part of the study protocol, or the prevalence of PE (P > 0.2 for all comparisons).

Publication Bias

We found no evidence of publication bias by examining funnel plots (data not shown) or by performing the Egger test (26)(overall VTE rate, P = 0.07; fatal PE, P > 0.2). Because tests for publication bias are relatively insensitive, we corrected for potential unpublished data by using the Duval and Tweedie (27) meta-trim method, which produced an adjusted overall PE rate of 1.1% (CI, 0.8% to 1.5%) and no change in the fatal PE rate.

Outcomes after Inconclusive, Nondiagnostic, or Suboptimal CTPA Results

Sixteen studies (3, 6, 1113, 15, 17, 19, 32, 34, 3842, 44) explicitly reported that 327 patients had CTPA results described as inconclusive, indeterminate, uninterpretable, nondiagnostic, or suboptimal. Seventy-four of these 327 patients, from 8 studies (3, 6, 12, 15, 32, 38, 4041), were classified separately. They were not excluded from the final analysis, did not receive anticoagulation empirically, and either underwent additional diagnostic evaluation or were followed clinically. Twelve patients (16.2%) subsequently received a diagnosis of VTE.

Our data suggest that it is safe to withhold anticoagulation in patients with negative results on CTPA. Our literature review and meta-analysis of 23 studies revealed that the 3-month rate of subsequent VTE after negative results on CTPA is very low (VTE, 1.4% [CI, 1.1% to 1.8%]; fatal PE, 0.51% [CI, 0.33% to 0.76%]). This low rate of recurrent VTE is similar to that seen after negative results on CPA (4546). In the Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED) study (45), the largest pre-CTPA study with outcome data, rates of subsequent VTE and fatal PE were 1.6% (CI, 0.3% to 2.9%) and 0.53% (CI, 0.16% to 1.9%), respectively. Van Beek and coworkers (46) performed a systematic review of all prospective trials (including PIOPED) that included outcome data on patients who did not receive anticoagulation after negative results on CPA. They reported summary rates of 1.7% (CI, 1.7% to 2.7%) for VTE and 0.30% (CI, 0.02% to 0.70%) for fatal PE.

Although CTPA for diagnosis of PE was first assessed in 1992 (47), recent literature reviews have concluded that sufficient evaluation of this method is still lacking (2122). The important missing piece of information is whether it is safe to withhold anticoagulation after negative CTPA results. Our findings suggest that rates of subsequent events in patients with negative CTPA results are similar to rates observed after negative results on CPA. Although CTPA has not been proven to be accurate as CPA, much of the literature on CTPA has used early-generation CT scanners with a limited number of detectors. More recent literature has shown that the use of multidetector CT scanners and more sophisticated reconstruction algorithms allows better identification of higher-generation pulmonary arteries and improved diagnostic yield (4852). In addition, multidetector scanners can perform image acquisition approximately twice as quickly as single-detector scanners and may reduce the number of technically inadequate studies (48). Nonetheless, our results suggest that even early-generation CTPA is safe for management of patients with suspected acute PE.

Two of the most methodologically robust prospective studies we reviewed combined CTPA with lower-extremity compression ultrasonography (3, 6). One of these studies reported, however, that the 3-month VTE recurrence rate would have been 1.3% if anticoagulation had been withheld only because of normal CTPA results (that is, if no lower-extremity compression ultrasonography had been performed) (3). Our sensitivity analysis did not show that the way CTPA was performed—alone or in combination—had any significant effect on the pooled rates of VTE and fatal PE. However, we did find that among patients who received anticoagulation despite negative CTPA results, 14% were treated because venous ultrasonography had revealed acute DVT. Had these patients been left untreated because of negative CTPA results, the subsequent VTE rate may have been slightly higher. Therefore, the role of CTPA without concomitant lower-extremity imaging is still undefined. Computed tomographic venography has shown promise as an adjunctive study when added to CTPA and may increase the diagnostic yield (5355); recent studies (5354) suggest that this test may be more sensitive at detecting DVT than concomitant lower-extremity ultrasonography.

Only 6 studies combined an assessment of clinical probability with imaging. Although the PIOPED study (45) demonstrated that a pretest clinical estimate of PE was very valuable in dictating management after lung scintigraphy, and although clinical prediction scoring systems for PE have been devised and validated (9, 5657), the influence of clinical pretest probability on dictating diagnostic strategy after negative results on “screening” CTPA is unknown. Furthermore, if CTPA were applied as a definitive study (a step our meta-analysis would support), any influence of pretest probability would not be important. Pretest probability assessments should be used to select patients for CTPA, since recent publications support the exclusion of PE based on a low pretest probability and negative results on d-dimer testing (711, 13).

Some of the included studies documented a high rate of subsequent VTE after inconclusive results on CTPA, although not all allowed extraction of these data. Criteria for nondiagnostic CTPA results, which varied among studies, were arguably subjective but were generally defined by a combination of insufficient contrast enhancement (for example, inadequate vessel clarity past the central pulmonary arteries), inter-reader variability, and technical considerations (for example, significant motion or imaging artifact). Nondiagnostic results after CTPA are not uncommon (13, 41, 44) and occur with frequency similar to that of nondiagnostic results on CPA (5859). However, CTPA results that are inconclusive for PE do not modify the prior probability of disease (6). It would be important to know whether the subsequent rate of VTE in this population correlated with the number of inconclusive studies, but we could not extract these data from the information provided by the primary authors. In our review, the cumulative rate of subsequent VTE among patients who had inconclusive CTPA results but did not receive anticoagulation was high (16.2%). This finding supports the recommendation that when a viable alternative diagnosis is not revealed incidentally, additional testing is indicated (6, 12). Improvements in technical quality (37, 60) and interpretation (61) of CTPA results may decrease the frequency of nondiagnostic results, but until such improvements are realized, CPA, repeated CTPA, or serial lower-extremity ultrasonography should be performed to confirm or exclude PE. Local resources and expertise should dictate study selection.

Studies included in our review had several important limitations. Our search was not limited to the English language but included only published studies. However, we could find no evidence of publication bias. Prospective studies used a variety of diagnostic algorithms, as detailed earlier. No two management strategies were identical, although we found no evidence of heterogeneity in outcomes between studies. Although a majority of studies (16) enrolled consecutive patients, there were some differences in patient selection. Autopsy or objective diagnostic testing was usually used to confirm recurrent VTE; however, clinical suspicion or adjudication committee opinion was used on occasion. Rarely, means of confirmation were not described. Follow-up was not complete in most studies.

In addition, CTPA techniques varied both across and within studies. Moreover, all studies used early-generation CT technology, and none of the studies used reconstruction algorithms for interpretation. Thus, our findings may not be directly applicable to patients imaged with variable-thickness scanning, although advances in data acquisition would probably improve outcomes after negative results on CTPA.

In sum, the rate of subsequent VTE after negative results on CTPA appears to be very low. We found that CTPA compares favorably with CPA as a definitive study to confirm or exclude PE. Ideally, a trial that randomly assigns patients to evaluation with CTPA versus CPA as the definitive diagnostic study, withholds anticoagulation in all patients with negative imaging results, and rigorously documents subsequent VTE events would provide clear guidance on the management of patients with suspected PE. However, given the very low rates of subsequent VTE previously documented in patients managed according to CPA results, as well as in patients managed with CTPA as we have shown here, such a trial would require the enrollment of more than 10 000 patients to detect a clinically significant difference in subsequent VTE rates. Therefore, it is unlikely to be performed. In the absence of such a trial or prospective trials examining clinical outcomes when CTPA is used as the sole diagnostic examination, imaging of the lower extremities (either lower-extremity ultrasonography or CT venography) should be performed concurrently. Withholding anticoagulation seems to be safe in patients managed in this way.

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Garg K, Welsh CH, Feyerabend AJ, Subber SW, Russ PD, Johnston RJ. et al.  Pulmonary embolism: diagnosis with spiral CT and ventilation-perfusion scanning—correlation with pulmonary angiographic results or clinical outcome. Radiology. 1998; 208:201-8. PubMed
 
Goodman LR, Lipchik RJ, Kuzo RS, Liu Y, McAuliffe TL, O'Brien DJ.  Subsequent pulmonary embolism: risk after a negative helical CT pulmonary angiogram—prospective comparison with scintigraphy. Radiology. 2000; 215:535-42. PubMed
 
Kavanagh EC, O'Hare A, Hargaden G, Murray JG.  Risk of pulmonary embolism after negative MDCT pulmonary angiography findings. AJR Am J Roentgenol. 2004; 182:499-504. PubMed
 
Lomis NN, Yoon HC, Moran AG, Miller FJ.  Clinical outcomes of patients after a negative spiral CT pulmonary arteriogram in the evaluation of acute pulmonary embolism. J Vasc Interv Radiol. 1999; 10:707-12. PubMed
 
Nilsson T, Olausson A, Johnsson H, Nyman U, Aspelin P.  Negative spiral CT in acute pulmonary embolism. Acta Radiol. 2002; 43:486-91. PubMed
 
Perrier A, Roy PM, Aujesky D, Chagnon I, Howarth N, Gourdier AL. et al.  Diagnosing pulmonary embolism in outpatients with clinical assessment, d-dimer measurement, venous ultrasound, and helical computed tomography: a multicenter management study. Am J Med. 2004; 116:291-9. PubMed
 
Remy-Jardin M, Remy J, Baghaie F, Fribourg M, Artaud D, Duhamel A.  Clinical value of thin collimation in the diagnostic workup of pulmonary embolism. AJR Am J Roentgenol. 2000; 175:407-11. PubMed
 
Remy-Jardin M, Tillie-Leblond I, Szapiro D, Ghaye B, Cotte L, Mastora I. et al.  CT angiography of pulmonary embolism in patients with underlying respiratory disease: impact of multislice CT on image quality and negative predictive value. Eur Radiol. 2002; 12:1971-8. PubMed
 
Swensen SJ, Sheedy PF 2nd, Ryu JH, Pickett DD, Schleck CD, Ilstrup DM. et al.  Outcomes after withholding anticoagulation from patients with suspected acute pulmonary embolism and negative computed tomographic findings: a cohort study. Mayo Clin Proc. 2002; 77:130-8. PubMed
 
Tillie-Leblond I, Mastora I, Radenne F, Paillard S, Tonnel AB, Remy J. et al.  Risk of pulmonary embolism after a negative spiral CT angiogram in patients with pulmonary disease: 1-year clinical follow-up study. Radiology. 2002; 223:461-7. PubMed
 
.  Value of the ventilation/perfusion scan in acute pulmonary embolism. Results of the prospective investigation of pulmonary embolism diagnosis (PIOPED). The PIOPED Investigators. JAMA. 1990; 263:2753-9. PubMed
 
van Beek EJ, Brouwerst EM, Song B, Stein PD, Oudkerk M.  Clinical validity of a normal pulmonary angiogram in patients with suspected pulmonary embolism—a critical review. Clin Radiol. 2001; 56:838-42. PubMed
 
Remy-Jardin M, Remy J, Wattinne L, Giraud F.  Central pulmonary thromboembolism: diagnosis with spiral volumetric CT with the single-breath-hold technique—comparison with pulmonary angiography. Radiology. 1992; 185:381-7. PubMed
 
Lawler LP, Fishman EK.  Multi-detector row CT of thoracic disease with emphasis on 3D volume rendering and CT angiography. Radiographics. 2001; 21:1257-73. PubMed
 
Qanadli SD, Hajjam ME, Mesurolle B, Barré O, Bruckert F, Joseph T. et al.  Pulmonary embolism detection: prospective evaluation of dual-section helical CT versus selective pulmonary arteriography in 157 patients. Radiology. 2000; 217:447-55. PubMed
 
Patel S, Kazerooni EA, Cascade PN.  Pulmonary embolism: optimization of small pulmonary artery visualization at multi-detector row CT. Radiology. 2003; 227:455-60. PubMed
 
Ghaye B, Szapiro D, Mastora I, Delannoy V, Duhamel A, Remy J. et al.  Peripheral pulmonary arteries: how far in the lung does multi-detector row spiral CT allow analysis? Radiology. 2001; 219:629-36. PubMed
 
Simon M, Boiselle PM, Choi JR, Rosen MP, Reynolds K, Raptopoulos V.  Paddle-wheel CT display of pulmonary arteries and other lung structures: a new imaging approach. AJR Am J Roentgenol. 2001; 177:195-8. PubMed
 
Loud PA, Katz DS, Bruce DA, Klippenstein DL, Grossman ZD.  Deep venous thrombosis with suspected pulmonary embolism: detection with combined CT venography and pulmonary angiography. Radiology. 2001; 219:498-502. PubMed
 
Cham MD, Yankelevitz DF, Shaham D, Shah AA, Sherman L, Lewis A. et al.  Deep venous thrombosis: detection by using indirect CT venography. The Pulmonary Angiography-Indirect CT Venography Cooperative Group. Radiology. 2000; 216:744-51. PubMed
 
Ghaye B, Dondelinger RF.  Non-traumatic thoracic emergencies: CT venography in an integrated diagnostic strategy of acute pulmonary embolism and venous thrombosis. Eur Radiol. 2002; 12:1906-21. PubMed
 
Wicki J, Perneger TV, Junod AF, Bounameaux H, Perrier A.  Assessing clinical probability of pulmonary embolism in the emergency ward: a simple score. Arch Intern Med. 2001; 161:92-7. PubMed
 
Chunilal SD, Eikelboom JW, Attia J, Miniati M, Panju AA, Simel DL. et al.  Does this patient have pulmonary embolism? JAMA. 2003; 290:2849-58. PubMed
 
Remy-Jardin M, Remy J.  Spiral CT angiography of the pulmonary circulation. Radiology. 1999; 212:615-36. PubMed
 
Stein PD, Athanasoulis C, Alavi A, Greenspan RH, Hales CA, Saltzman HA. et al.  Complications and validity of pulmonary angiography in acute pulmonary embolism. Circulation. 1992; 85:462-8. PubMed
 
Remy-Jardin M, Remy J, Artaud D, Deschildre F, Duhamel A.  Peripheral pulmonary arteries: optimization of the spiral CT acquisition protocol. Radiology. 1997; 204:157-63. PubMed
 
Remy-Jardin M, Remy J, Artaud D, Deschildre F, Fribourg M, Beregi JP.  Spiral CT of pulmonary embolism: technical considerations and interpretive pitfalls. J Thorac Imaging. 1997; 12:103-17. PubMed
 

Figures

Grahic Jump Location
Figure 1.
Flow diagram of study selection.

CTPA = computed tomographic pulmonary angiography; PE = pulmonary embolism.

Grahic Jump Location
Grahic Jump Location
Figure 2.
Forest plots of total venous thromboembolism (VTE) events (top) and fatal pulmonary embolism (PE) events (bottom).

The number of patients for each study is the number of patients eligible for outcome assessment, and the event rates are a combination of recurrent VTE and fatal PE (see Table). Values in parentheses on the right-hand side of the figure are the upper bound of the CI unless otherwise indicated.

Grahic Jump Location

Tables

Table Jump PlaceholderTable.  Data Extracted from Individual Studies
Table Jump PlaceholderAppendix Table.  Quality Ratings of Included Studies

References

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Mayo JR, Remy-Jardin M, Müller NL, Remy J, Worsley DF, Hossein-Foucher C. et al.  Pulmonary embolism: prospective comparison of spiral CT with ventilation-perfusion scintigraphy. Radiology. 1997; 205:447-52. PubMed
 
Cross JJ, Kemp PM, Walsh CG, Flower CD, Dixon AK.  A randomized trial of spiral CT and ventilation perfusion scintigraphy for the diagnosis of pulmonary embolism. Clin Radiol. 1998; 53:177-82. PubMed
 
Ferretti GR, Ayanian D, Ranchoup Y, Thony F, Bosson JL, Coulomb M.  [CT x-ray evaluation of abdominal and pelvic veins in patients suspected of acute pulmonary embolism with negative Doppler sonography]. J Radiol. 1998; 79:327-30. PubMed
 
Ferretti GR, Bosson JL, Buffaz PD, Ayanian D, Pison C, Blanc F. et al.  Acute pulmonary embolism: role of helical CT in 164 patients with intermediate probability at ventilation-perfusion scintigraphy and normal results at duplex US of the legs. Radiology. 1997; 205:453-8. PubMed
 
Blachere H, Latrabe V, Montaudon M, Valli N, Couffinhal T, Raherisson C. et al.  Pulmonary embolism revealed on helical CT angiography: comparison with ventilation-perfusion radionuclide lung scanning. AJR Am J Roentgenol. 2000; 174:1041-7. PubMed
 
Bourriot K, Couffinhal T, Bernard V, Montaudon M, Bonnet J, Laurent F.  Clinical outcome after a negative spiral CT pulmonary angiographic finding in an inpatient population from cardiology and pneumology wards. Chest. 2003; 123:359-65. PubMed
 
Garg K, Sieler H, Welsh CH, Johnston RJ, Russ PD.  Clinical validity of helical CT being interpreted as negative for pulmonary embolism: implications for patient treatment. AJR Am J Roentgenol. 1999; 172:1627-31. PubMed
 
Garg K, Welsh CH, Feyerabend AJ, Subber SW, Russ PD, Johnston RJ. et al.  Pulmonary embolism: diagnosis with spiral CT and ventilation-perfusion scanning—correlation with pulmonary angiographic results or clinical outcome. Radiology. 1998; 208:201-8. PubMed
 
Goodman LR, Lipchik RJ, Kuzo RS, Liu Y, McAuliffe TL, O'Brien DJ.  Subsequent pulmonary embolism: risk after a negative helical CT pulmonary angiogram—prospective comparison with scintigraphy. Radiology. 2000; 215:535-42. PubMed
 
Kavanagh EC, O'Hare A, Hargaden G, Murray JG.  Risk of pulmonary embolism after negative MDCT pulmonary angiography findings. AJR Am J Roentgenol. 2004; 182:499-504. PubMed
 
Lomis NN, Yoon HC, Moran AG, Miller FJ.  Clinical outcomes of patients after a negative spiral CT pulmonary arteriogram in the evaluation of acute pulmonary embolism. J Vasc Interv Radiol. 1999; 10:707-12. PubMed
 
Nilsson T, Olausson A, Johnsson H, Nyman U, Aspelin P.  Negative spiral CT in acute pulmonary embolism. Acta Radiol. 2002; 43:486-91. PubMed
 
Perrier A, Roy PM, Aujesky D, Chagnon I, Howarth N, Gourdier AL. et al.  Diagnosing pulmonary embolism in outpatients with clinical assessment, d-dimer measurement, venous ultrasound, and helical computed tomography: a multicenter management study. Am J Med. 2004; 116:291-9. PubMed
 
Remy-Jardin M, Remy J, Baghaie F, Fribourg M, Artaud D, Duhamel A.  Clinical value of thin collimation in the diagnostic workup of pulmonary embolism. AJR Am J Roentgenol. 2000; 175:407-11. PubMed
 
Remy-Jardin M, Tillie-Leblond I, Szapiro D, Ghaye B, Cotte L, Mastora I. et al.  CT angiography of pulmonary embolism in patients with underlying respiratory disease: impact of multislice CT on image quality and negative predictive value. Eur Radiol. 2002; 12:1971-8. PubMed
 
Swensen SJ, Sheedy PF 2nd, Ryu JH, Pickett DD, Schleck CD, Ilstrup DM. et al.  Outcomes after withholding anticoagulation from patients with suspected acute pulmonary embolism and negative computed tomographic findings: a cohort study. Mayo Clin Proc. 2002; 77:130-8. PubMed
 
Tillie-Leblond I, Mastora I, Radenne F, Paillard S, Tonnel AB, Remy J. et al.  Risk of pulmonary embolism after a negative spiral CT angiogram in patients with pulmonary disease: 1-year clinical follow-up study. Radiology. 2002; 223:461-7. PubMed
 
.  Value of the ventilation/perfusion scan in acute pulmonary embolism. Results of the prospective investigation of pulmonary embolism diagnosis (PIOPED). The PIOPED Investigators. JAMA. 1990; 263:2753-9. PubMed
 
van Beek EJ, Brouwerst EM, Song B, Stein PD, Oudkerk M.  Clinical validity of a normal pulmonary angiogram in patients with suspected pulmonary embolism—a critical review. Clin Radiol. 2001; 56:838-42. PubMed
 
Remy-Jardin M, Remy J, Wattinne L, Giraud F.  Central pulmonary thromboembolism: diagnosis with spiral volumetric CT with the single-breath-hold technique—comparison with pulmonary angiography. Radiology. 1992; 185:381-7. PubMed
 
Lawler LP, Fishman EK.  Multi-detector row CT of thoracic disease with emphasis on 3D volume rendering and CT angiography. Radiographics. 2001; 21:1257-73. PubMed
 
Qanadli SD, Hajjam ME, Mesurolle B, Barré O, Bruckert F, Joseph T. et al.  Pulmonary embolism detection: prospective evaluation of dual-section helical CT versus selective pulmonary arteriography in 157 patients. Radiology. 2000; 217:447-55. PubMed
 
Patel S, Kazerooni EA, Cascade PN.  Pulmonary embolism: optimization of small pulmonary artery visualization at multi-detector row CT. Radiology. 2003; 227:455-60. PubMed
 
Ghaye B, Szapiro D, Mastora I, Delannoy V, Duhamel A, Remy J. et al.  Peripheral pulmonary arteries: how far in the lung does multi-detector row spiral CT allow analysis? Radiology. 2001; 219:629-36. PubMed
 
Simon M, Boiselle PM, Choi JR, Rosen MP, Reynolds K, Raptopoulos V.  Paddle-wheel CT display of pulmonary arteries and other lung structures: a new imaging approach. AJR Am J Roentgenol. 2001; 177:195-8. PubMed
 
Loud PA, Katz DS, Bruce DA, Klippenstein DL, Grossman ZD.  Deep venous thrombosis with suspected pulmonary embolism: detection with combined CT venography and pulmonary angiography. Radiology. 2001; 219:498-502. PubMed
 
Cham MD, Yankelevitz DF, Shaham D, Shah AA, Sherman L, Lewis A. et al.  Deep venous thrombosis: detection by using indirect CT venography. The Pulmonary Angiography-Indirect CT Venography Cooperative Group. Radiology. 2000; 216:744-51. PubMed
 
Ghaye B, Dondelinger RF.  Non-traumatic thoracic emergencies: CT venography in an integrated diagnostic strategy of acute pulmonary embolism and venous thrombosis. Eur Radiol. 2002; 12:1906-21. PubMed
 
Wicki J, Perneger TV, Junod AF, Bounameaux H, Perrier A.  Assessing clinical probability of pulmonary embolism in the emergency ward: a simple score. Arch Intern Med. 2001; 161:92-7. PubMed
 
Chunilal SD, Eikelboom JW, Attia J, Miniati M, Panju AA, Simel DL. et al.  Does this patient have pulmonary embolism? JAMA. 2003; 290:2849-58. PubMed
 
Remy-Jardin M, Remy J.  Spiral CT angiography of the pulmonary circulation. Radiology. 1999; 212:615-36. PubMed
 
Stein PD, Athanasoulis C, Alavi A, Greenspan RH, Hales CA, Saltzman HA. et al.  Complications and validity of pulmonary angiography in acute pulmonary embolism. Circulation. 1992; 85:462-8. PubMed
 
Remy-Jardin M, Remy J, Artaud D, Deschildre F, Duhamel A.  Peripheral pulmonary arteries: optimization of the spiral CT acquisition protocol. Radiology. 1997; 204:157-63. PubMed
 
Remy-Jardin M, Remy J, Artaud D, Deschildre F, Fribourg M, Beregi JP.  Spiral CT of pulmonary embolism: technical considerations and interpretive pitfalls. J Thorac Imaging. 1997; 12:103-17. PubMed
 

Letters

NOTE:
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Comments

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Using CTPA to Diagnose Pulmonary Embolism
Posted on December 7, 2004
Shaun D Frost
HealthPartners Medical Group and Clinics, Minneapolis, MN
Conflict of Interest: None Declared

I am concerned that the article by Moores and colleagues (1) conveys an ambiguous message about the utility of spiral computed tomographic pulmonary angiography (CTPA) for diagnosing pulmonary embolism (PE). The ambiguity results from seemingly different conclusions in the abstract, discussion, and editors' synopsis sections of the manuscript. The authors conclude their discussion by stating that withholding anticoagulation seems to be safe in patients managed by negative results on CTPA performed concurrently with imaging of the lower extremities (either ultrasonography or CT venography). The abstract that accompanies the manuscript however fails to mention the importance of concurrent lower extremity imaging, stating only "it appears to be safe to withhold anticoagulation after negative CTPA results." The editors' synopsis also fails to mention lower extremity imaging, yet adds that concurrent clinical probability assessment is necessary by stating "withholding anticoagulation from patients with low to moderate probability of PE and negative results on CTPA appears reasonable".

These incongruences are not trivial. Given that busy clinicians often only read the abstract and editors' synopsis sections of a manuscript, every effort should be made to ensure that these sections accurately reflect the authors' conclusions. As this pertains to the article by Moores and colleagues, clinicians who read only the abstract may conclude that a negative CTPA can function as the sole diagnostic test for ruling out PE. Diagnostic strategies based on this erroneous conclusion will exclude lower extremity imaging and clinical probability estimation, and subsequently some patients with venous thrombosis may not be diagnosed or treated.

References 1. Moores L, Jackson W, Shorr A, Jackson J. Meta-analysis: outcomes in patients with suspected pulmonary embolism managed with computed tomographic pulmonary angiography. Ann Intern Med. 2004;141:866-874.

Conflict of Interest:

None declared

CT pulmonary angiography and suspected pulmonary embolism: a word of caution
Posted on December 11, 2004
Philippe Girard
Institut Mutualiste Montsouris, Paris, France
Conflict of Interest: None Declared

In their careful and commendable meta-analysis of outcome studies that used CT pulmonary angiography (CTPA) in patients with suspected pulmonary embolism (PE), Moores and colleagues conclude that "it appears to be safe to withhold anticoagulation after negative CTPA results". I believe that such a message goes beyond the conclusions that can be drawn from the authors' data. As acknowledged by the authors, among the 23 outcome studies they analyzed, only one used CTPA as the sole diagnostic test. Further, in the three largest prospective studies (at least 350 patients in each study remained untreated), anticoagulation was withheld only when both CTPA and compression ultrasonography (CUS) of the lower limbs were negative(1-3). When it could be calculated, the prevalence of DVT detected by CUS in patients with negative CTPA results was very low (0.8%) in one study (3), but it was significantly higher in 2 other studies (7.7% and 8.4%, respectively(1, 4)), and it reached 18.8% in a study of 117 hospitalized patients(5). Therefore, until specific outcome studies demonstrate the opposite, using CTPA as the sole diagnostic test to withhold anticoagulation in patients with suspected PE should be considered unwise, not "safe".

1. Musset D, Parent F, Meyer G, et al. Diagnostic strategy for patients with suspected pulmonary embolism: a prospective multicentre outcome study. Lancet. 2002;360(9349):1914-1920. 2. Perrier A, Roy PM, Aujesky D, et al. Diagnosing pulmonary embolism in outpatients with clinical assessment, D-dimer measurement, venous ultrasound, and helical computed tomography: a multicenter management study. Am J Med. 2004;116(5):291-9. 3. van Strijen MJ, de Monye W, Schiereck J, et al. Single-detector helical computed tomography as the primary diagnostic test in suspected pulmonary embolism: a multicenter clinical management study of 510 patients. Ann Intern Med. 2003;138(4):307-14. 4. Perrier A, Howarth N, Didier D, et al. Performance of helical computed tomography in unselected outpatients with suspected pulmonary embolism. Ann Intern Med. 2001;135(2):88-97. 5. Bourriot K, Couffinhal T, Bernard V, Montaudon M, Bonnet J, Laurent F. Clinical outcome after a negative spiral CT pulmonary angiographic finding in an inpatient population from cardiology and pneumology wards. Chest. 2003;123(2):359-65.

Conflict of Interest:

None declared

CT Pulmonary Angiography should be part of a diagnostic strategy for pulmonary embolism.
Posted on December 24, 2004
Pieter W. Kamphuisen
Division of Internal and Cardiovascular Medicine, University of Perugia, Italy
Conflict of Interest: None Declared

Contrast-enhanced spiral computed tomography (CTPA) is becoming the preferred diagnostic test for suspected acute pulmonary embolism (PE) in many hospitals. Based on their meta-analysis Moores et al. (1) conclude that it appears to be safe to withhold anticoagulant therapy after a negative CTPA in patients with suspected PE. This may imply that CTPA could be used as the first and sole diagnostic test in these patients. We believe that this conclusion is premature for two different reasons. First, in consecutive patients with suspected PE the sensitivity of CTPA is only 70% and the negative likelihood ratio is 0.3 (2). This likelihood ratio is comparable to that of a low probability lung scan, a diagnostic result considered insufficient to safely exclude PE. The sensitivity of CTPA is only 30% for detection of isolated subsegmental emboli (3). These isolated subsegmental emboli are present in up to 30% of patients with documented PE and their clinical significance cannot be excluded. Second, CTPA should be part of a diagnostic strategy for the diagnosis of PE and not be the sole diagnostic test. The combination of a low clinical probability score and a normal d-dimer level has been shown to safely exclude PE in 20-30% of patients (4). Therefore, using such an approach will prevent 20-30% of the patients from further diagnostic testing. Placing CTPA in the second round of a diagnostic strategy will reduce costs and radiation exposure. The low risk patients will be filtered by a highly accurate, simple and cheap strategy. In the remaining high risk patients, including patients with high d-dimer levels or high clinical probability, CTPA can be performed to confirm the diagnosis of PE or establish an alternative diagnosis. Thus, since the diagnostic accuracy of excluding PE using CTPA seems sub- optimal and this test is relatively expensive, CTPA should not be used as the first diagnostic test in patients with suspected PE, but must be implemented in a diagnostic strategy, which begins with clinical probability and d-dimer assessment.

1. Moores LK, Jackson Jr. WL, Shorr AF, Jackson JL. Meta-Analysis: Outcomes in Patients with Suspected Pulmonary Embolism Managed with Computed Tomographic Pulmonary Angiography. Ann Intern Med 2004;141:866- 874. 2. Perrier A, Howarth N, Didier D, Loubeyre P, Unger PF, de Moerloose P, et al. Performance of helical computed tomography in unselected outpatients with suspected pulmonary embolism. Ann Intern Med 2001;135:88- 97. 3. Goodman LR, Curtin JJ, Mewissen MW, Foley WD, Lipchik RJ, Crain MR, et al. Detection of pulmonary embolism in patients with unresolved clinical and scintigraphic diagnosis: helical CT versus angiography. AJR Am J Roentgenol 1995;164:1369-74. 4. Stein PD, Hull RD, Patel KC, Olson RE, Ghali WA, Brant R, et al. D- dimer for the exclusion of acute venous thrombosis and pulmonary embolism: a systematic review. Ann Intern Med 2004;140:589-602.

Conflict of Interest:

None declared

The Applicability of a Negative Computed Tomographic Pulmonary Angiogram in Clinical Practice
Posted on January 20, 2005
Jeremy P Smith
Northwestern University
Conflict of Interest: None Declared

Moores and colleagues state in their discussion that "Our data suggest that it is safe to withhold anticoagulation in patients with negative results on CTPA." There are two problems with this conclusion. The first is that almost all the studies included in the meta-analysis involved additional testing before discharging patients without anticoagulation, e.g. negative Duplex ultrasonography or non-diagnostic ventilation/perfusion scans. These results would serve to create a pool of patients with lower likelihood of occult PE as compared to patients who had simply one negative CTPA. One therefore cannot derive, from this data, the conclusion that it is safe to withhold anticoagulation in patients with negative CTPA in the absence of additional testing.

The second problem is that a significant percentage of patients in these studies did receive anticoagulation, occasionally because the clinical probability for PE remained high despite a negative CTPA. Moores and colleagues exclude these patients from their analysis of outcomes, but one cannot then extrapolate from this outcome data that it is safe to withhold anticoagulation in patients with negative CTPA. The only safe conclusion would be that it is safe to withhold anticoagulation in patients with negative CTPA who have no other indication for anticoagulation (including high suspicion of PE).

Conflict of Interest:

None declared

Defining the Role of CTPA in Suspected Pulmonary Embolism
Posted on February 8, 2005
Lisa K Moores
Uniformed Services University of the Health Sciences
Conflict of Interest: None Declared

IN RESPONSE: We appreciate the comments regarding our meta-analysis (1) and the opportunity to clarify our conclusion. As stated in the discussion, "the role of CTPA without concomitant lower-extremity imaging is still undefined" (1). We agree with both Dr. Frost and Dr. Girard that the literature to date does not support definitive exclusion of VTE with CTPA alone, and we recommend concurrent lower-extremity imaging before withholding anticoagulation in patients with suspected clot. While advancements in imaging technology may eventually improve diagnostic accuracy of CTPA and allow for a single test, in our opinion further study is required before this can be recommended. Moreover, the emergence of simultaneous CT venography might ultimately permit rapid, accurate assessment of the lower extremities in a combined, single-modality study (2-5), rendering moot the role of isolated imaging of the chest in VTE. We agree with both Dr. Frost and Dr. Girard that our abstract should have been written more explicitly to match our ultimate conclusions.

In response to Dr. Kamphuisen, we did not endorse CTPA as an initial diagnostic test. On the contrary, we acknowledged that "pretest probability assessments should be used to select patients for CTPA, since recent publications support the exclusion of PE based on a low pretest probability and negative results on D-dimer testing" (1).

William L. Jackson, Jr., MD Lisa K. Moores, MD Walter Reed Army Medical Center Washington, DC 20307

The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the Department of the Army or the Department of Defense.

1. Moores LK, Jackson WL Jr, Shorr AF, Jackson JL. Meta-analysis: outcomes in patients with suspected pulmonary embolism managed with computed tomography pulmonary angiography. Ann Intern Med 2004;141:866- 874.

2. Loud PA, Katz DS, Bruce DA, Klippenstein DL, Grossman ZD. Deep venous thrombosis with suspected pulmonary embolism: detection with combined CT venography and pulmonary angiography. Radiology. 2001;219:498- 502.

3. Cham MD, Yankelevitz DF, Shaham D, Shah AA, Sherman L, Lewis A, et al. Deep venous thrombosis: detection by using indirect CT venography. The Pulmonary Angiography-Indirect CT Venography Cooperative Group. Radiology. 2000;216:744-51.

4. Ghaye B, Dondelinger RF. Non-traumatic thoracic emergencies: CT venography in an integrated diagnostic strategy of acute pulmonary embolism and venous thrombosis. Eur Radiol. 2002;12:1906-21.

5. Lim KE, Hsu YY, Hsu WC, Huang CC. Combined computed tomography and venography and pulmonary angiography for the diagnosis of PE and DVT in the ED. Am J Emerg Med. 2004;22:301-6.

Conflict of Interest:

None declared

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