Emerg Radiol DOI 10.1007/s10140-013-1169-x
ORIGINAL ARTICLE
The yield of CT pulmonary angiograms to exclude acute pulmonary embolism Andreu F. Costa & Hamed Basseri & Adnan Sheikh & Ian Stiell & Carole Dennie
Received: 27 August 2013 / Accepted: 9 October 2013 # Am Soc Emergency Radiol 2013
Abstract There is accumulating evidence regarding the overuse of computed tomography pulmonary angiography (CTPA) to exclude pulmonary embolism (PE). We evaluated the yield of CTPA studies performed at our tertiary care hospital between April 2008 and March 2010 for emergency patients (ED), inpatients (INPT), and intensive care unit inpatients (ICU). For each patient group, we also compared CTPA positivity rates among the following: daytime and on-call studies, 1 year before and after institution of an Emergency Radiology division, interpreting thoracic and non-thoracic radiologists, and individual emergency physicians. Patients with a history of PE and indeterminate studies were excluded. The diagnosis of PE was based on the radiology report. D-dimer values obtained within 24 h prior to CTPA were recorded. A total of 3,571/4,757 CTPA studies satisfied the inclusion criteria. The fraction of positive studies was 252/1,677 (15.0 %) ED, 255/1,548 (16.5 %) INPT, and 62/346 (17.9 %) ICU. There was no difference in yield between patient groups, daytime vs. on-call studies, before vs. after instituting an emergency radiology division, and thoracic vs. non-thoracic radiologists (p >0.05). For individual emergency physicians, A. F. Costa (*) : A. Sheikh : C. Dennie Department of Medical Imaging, The Ottawa Hospital, Civic Campus, 1053 Carling Avenue, Ottawa, Ontario K1Y 4E9, Canada e-mail: [email protected] A. F. Costa : H. Basseri : A. Sheikh : C. Dennie Department of Radiology, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada I. Stiell Department of Emergency Medicine, The Ottawa Hospital, Ottawa, Ontario, Canada I. Stiell Ottawa Hospital Research Institute, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada
the mean CTPA positivity rate was 15.4 % but varied considerably (σ =8.5 %, range, 0–38.5 %). In comparison to other recent studies, our yield of ED CTPA is relatively high but varied widely among individual emergency physicians. While the reasons for such differences require further investigation, our results reinforce the importance of a strong clinical assessment in the work-up of suspected PE. Keywords Computed tomography pulmonary angiography . Pulmonary embolism . Emergency medicine . D-dimer
Introduction Computed tomography pulmonary angiography (CTPA) is often the first-line imaging test for excluding pulmonary embolism (PE); it is accurate, fast, readily available and provides ancillary findings and alternative diagnoses. Withholding anticoagulation after a negative CTPA is associated with a very low risk of significant venous thromboembolic disease in the near future [1–6]. In most clinical situations, the advantages of CTPA are considered to outweigh the drawbacks of ionizing radiation, use of iodinated contrast, and health care cost. However, recent studies have presented other potential disadvantages of CTPA. These include the overdiagnosis of clinically irrelevant PE [6–10], decreased specificity and interobserver agreement in detecting subsegmental PE [11–14], and a high prevalence of incidental findings requiring clinical or imaging follow-up [15, 16]. Perhaps the most important issue with CTPA is the growing body of evidence regarding its overuse [17–20] and concomitant low yield. Several studies report positivity rates of less than 10 %, raising concerns about whether CTPA is being inappropriately used to exclude PE [15–18, 21–23]. Indeed, studies show that ordering physicians [17, 18, 20, 24, 25] make suboptimal use of validated clinical algorithms to assess for PE, such as the modified Wells criteria [26, 27],
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despite recommendations to the contrary by many expert groups including the Fleischner Society [28] and PIOPED II investigators [29]. The issues surrounding CTPA have led to imaging strategies and arguments [22, 30, 31] against CTPA as a first-line tool for excluding PE. Given the opposing trends of increasing use and decreasing yield, the objectives of this study were to perform a large health record review of CTPA studies performed at our institution over a 2-year period, compare our positivity rates with the literature, and assess for any differences in yield among the following subgroups: emergency patients (ED), inpatients (INPT), and intensive care unit inpatients (ICU), daytime and on-call studies, before and after institution of an Emergency Radiology division, interpreting thoracic and non-thoracic radiologists, and individual referring emergency physicians.
the CTPA study; as in other studies [18, 25], D-dimer values obtained outside this window were disregarded. The D-dimer used at our institution is an automated and fully quantitative, latex-enhanced immunoassay (Instrumentation Laboratory Company, Bedford, MA, USA) and is considered positive when greater than 300 μg/L and negative otherwise. An indeterminate D-dimer result, such as a hemolyzed sample, was considered equivalent to not performing the test if a repeat sample was not obtained. Emergency patients with negative D-dimer and positive CTPA studies were investigated further by obtaining a retrospective Wells score from the electronic health record, as well as the size and location of pulmonary emboli from the CTPA images. CTPA imaging and protocol
Materials and methods Patient data collection This study was Freedom of Information and Protection of Privacy Act (FIPPA) compliant and approved by our research ethics board; as this was a health record study, patient consent was not required. The study was conducted at a large tertiary care, adult teaching hospital in Canada that receives over 124, 000 emergency visits annually. We reviewed all CTPA studies performed on emergency department and admitted patients between April 1, 2008 and March 31, 2010 inclusively. Exclusion criteria were as follows: any non-emergency outpatient study, patients with a history of PE including chronic PE, CTPA studies performed after PE was incidentally diagnosed on another imaging test, any CTPA study not performed to rule out PE (e.g., vascular malformation), and any indeterminate CTPA study. The following characteristics of CTPA studies were obtained from the hospital picture archiving and communication system: patient age and sex, date and timestamp of study, referring physician, reporting radiologist, patient location (emergency, ICU, or non-ICU), and CTPA test result based on the final radiology report (positive, negative, or indeterminate). Note that CTPA studies where segmental or subsegmental PE could not be excluded were still classified as negative or positive, based on the radiologist's impression. Indeterminate studies were classified as such when the study was non-diagnostic or when the radiologist recommended further testing, such as a repeat CTPA, ventilation–perfusion scan, or lower extremity ultrasound. D-dimer Each patient's electronic health record was searched for a serum D-dimer value obtained within 24 h prior to undergoing
CTPA studies varied in protocol and were performed on GE (General Electric Medical Systems, Milwaukee, WI, USA) and Toshiba (Toshiba Medical Systems, Otawara Japan) scanners: GE 64 detector VCT (0.625-mm helical acquisition with 1.25-mm consecutive axial reconstructions), GE LightSpeed 16 (0.625-mm helical acquisition with 1.25-mm axial reconstructions), GE LightSpeed Plus (0.625-mm helical acquisition with 2.5-mm axial reconstructions at 1.25-mm interval), Toshiba Aquilion ONE (0.5-mm helical acquisition with 1.0-mm consecutive axial reconstructions), and Toshiba Aquilion 64 (0.5-mm helical acquisition with 1.0-mm consecutive axial reconstructions). Between 60 and 120 mL of iopamidol (Isovue-370, Bracco Diagnostics Inc., Princeton, NJ, USA) was injected at a rate of 4–5 cm3/s using an automated, computer-controlled device triggered by timing and threshold software. Radiologists Of the 35 interpreting radiologists, 27 were board-certified by the Royal College of Physicians and Surgeons of Canada and/ or the American Board of Radiology. Eight radiologists trained outside North America and worked under an academic license. Two radiologists were not fellowship trained; all others were subspecialized in one of thoracic, abdominopelvic, musculoskeletal, women's imaging, or interventional radiology. We collected data from the April 2008 to March 2010 time frame specifically to assess for any changes before and after institution of an Emergency Radiology division in April 2009. Prior to April 2009, imaging studies at our institution were assigned by radiological subspecialty; as such, CTPA studies were interpreted by thoracic radiologists during routine working hours. The Emergency Radiology division was created to improve wait times and expedite patient care in the Emergency Department; after April 2009, a non-thoracic
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radiologist reported all emergency patient CTPA studies during routine working hours. We obtained a full year of data before and after the Emergency Radiology division started to assess for any changes in CTPA ordering practices and yield, as well as CTPA reporting practices by thoracic vs. nonthoracic radiologists.
of clinical hours worked by each emergency physician over the 2-year study period was obtained. These data were used to normalize the number of CTPA studies ordered by each physician. Physicians who ordered fewer than 10 CTPA studies in the 2-year period were excluded from analysis. Statistical analysis
Patient data analysis Data analysis was performed using MATLAB (R2011a, Natick, MA, USA) and GraphPad Prism (5.00, La Jolla, CA, USA). For all patient data analyses, data were divided into three patient groups: ED, INPT, and ICU. Each patient group was analyzed for the number of positive and negative CTPA acquired during the following periods of interest: (1) the entire study period, April 2008 to March 2010; (2) routine working hours (Monday to Friday, 0800–1700 h) and on call (Monday to Friday, 1700–0800 h, and all day on weekends and holidays); and (3) the first (April 2008 to March 2009) and second (April 2009 to March 2010) years of interest, before and after institution of the Emergency Radiology division. To assess for any trend over time, comparison between the first and second years of CTPA data was also made by performing a linear regression of monthly ordering and positivity rates for each patient group in each year. To assess for any diurnal trend in CTPA ordering, a histogram was made of the CTPA study timestamps for each patient group, binned in 2-h timeslots throughout the day (0800–1000 h, 1000–1200 h, etc.). Radiologist data analysis The number of positive and negative CTPA studies reported by thoracic and non-thoracic radiologists was recorded for each patient group as well as for the entire cohort. Radiologists who interpreted fewer than 10 CTPA studies over the 2-year period were excluded from analysis.
Statistical analysis was performed using GraphPad Prism. The mean ages of each patient group were compared using the one-way analysis of variance (one-way ANOVA), and the variances were compared using Bartlett's test. Statistical comparison between each CTPA characteristic of interest was performed using the chi-square test.
Results A flowchart of included and excluded CTPA studies is presented in Fig. 1; note that only one exclusion criterion is counted per study, although multiple criteria may have applied. A total of 4,757 CTPA studies were performed during the study period; of these, 1,186 were excluded, leaving 3,571 studies. Patient groups A summary of patient and reporting radiologist results for each patient group is provided in Table 1. The number of included ED, INPT, and ICU CTPA studies was 1,677 (47 %), 1,548 (43.3 %), and 346 (9.7 %), respectively. The mean age in years and percentage of females (in parentheses) for each group were 60.4 (56.5 %) ED, 64.9 (55.5 %) INPT, and 61.5 (52.0 %) ICU. The mean ages were significantly different from each other (one-way ANOVA, p 0.05). The only series with a statistically significant non-zero slope was the ED CTPA ordering rate in the second year (p =0.007). Interpreting radiologists Thirty-one radiologists interpreted at least 10 CTPA studies over the 2-year study period. Thoracic radiologists interpreted approximately twice as many INPT and ICU CTPA studies as non-thoracic radiologists: 1,090 vs. 453 for INPT and 229 vs. 116 for ICU. For ED studies, the pattern was generally reversed: 630 vs. 1,045. There was no statistical difference in the number of positive CTPA studies interpreted by thoracic and non-thoracic radiologists for any of the patient groups (p =0.94, 0.55, and 0.77 for ED, INPT, and ICU, respectively), nor for the entire cohort combined (p =0.95).
Table 2 presents the number of positive, negative, and unavailable serum D-dimer values for each patient group according to CTPA result, positive or negative. Although the true performance of D-dimer cannot be assessed from our data because the number of true and false negatives is unknown (most patients with negative D-dimer would not have been evaluated further with CTPA), a subgroup of 913 emergency patients underwent both CTPA and D-dimer testing. In this subgroup, the D-dimer sensitivity was 97.9 % (95 % CI 94.0– 99.6) and the negative and positive predictive values (NPV and PPV) were 98.4 % (95 % CI 95.3–99.7) and 19.0 % (95 % CI 16.2–22.1), respectively. In the same subset, there were 182/913 (19.9 %) emergency patients who underwent CTPA despite a negative D-dimer, and only three of these CTPA studies were positive (1.6 %). Of the three patients with negative D-dimer and positive CTPA, all were of moderate pretest probability and had small PEs in the segmental or subsegmental pulmonary artery branches. Interestingly, each patient had strong risk factors for possible thrombosis: one patient was subsequently diagnosed with heterozygous factor V Leiden thrombophilia, another had a history of long-term immobility at home after being discharged from the hospital for subdural hemorrhage, and the third patient was undergoing chemotherapy for diffuse metastatic colorectal cancer.
Discussion Our results showed no significant difference in the yield of CTPA among emergency patients, inpatients, and ICU patients. Although we found that the annual CTPA positivity
Emerg Radiol Table 2 D-dimer results according to patient location and CTPA test result
ED, positive CTPA ED, negative CTPA INPT, positive CTPA INPT, negative CTPA ICU, positive CTPA ICU, negative CTPA
D-dimer positive
D-dimer negative
D-dimer not acquired
139 (8.3 %) 592 (35.3 %) 41 (2.6 %) 128 (8.3 %) 4 (1.2 %) 23 (6.6 %)
3 (0.2 %) 179 (10.7 %) 1 (0.1 %) 16 (1.0 %) 0 (0 %) 3 (0.9 %)
110 (6.6 %) 654 (39.0 %) 213 (13.8 %) 1,149 (74.2 %) 58 (16.8 %) 258 (74.6 %)
CTPA computed tomography pulmonary angiogram, ED emergency department patient, ICU intensive care unit inpatient, INPT non-ICU inpatient
Fig. 5 In these vertical bar graphs, each bar corresponds to 1 of 44 individual emergency physicians, and the same physician is represented at the same location on the x-axis in parts a, b, and c. a Total number of CTPA studies ordered by each emergency physician over the 2-year study period. b CTPA studies ordered normalized according to thousands of clinical hours worked by each emergency physician. c CTPA positivity rate for each emergency physician, that is, the number of positive CTPA studies divided by the total number of CTPA ordered for each emergency physician. CTPA computed tomography pulmonary angiogram
rate decreased for each patient group following institution of the Emergency Radiology division, these results were also not statistically significant. However, we discovered a substantial drop in positive ED CTPA studies (16.9 vs. 13.6 %, p =0.06) and significantly increasing monthly ED CTPA ordering rates in the second year (Fig. 4). We are currently investigating the
yield of other emergency patient imaging studies, as well as expanding our CTPA database, to assess whether emergency physicians have become more inclined to order imaging tests following institution of the Emergency Radiology division. Our chart review of the yield and characteristics of CTPA imaging is one of the largest and longest-spanning to date. Shown in Table 3 are CTPA positivity rates reported or derived from similar studies performed over the last decade. Interestingly, the highest CTPA positivity rates were found in the US and Canadian PIOPED II study [32], the Dutch Christopher study [1], and a Swiss and French study [2]. These were multicenter, prospective cohort trials that mandated all patients with suspected PE to be evaluated with the Wells, modified Wells, or Geneva criteria, respectively. Therefore, these landmark trials do not reflect actual clinical practice but rather ideal work-up protocol. Table 3 shows that, whereas the yield of inpatient CTPA is generally comparable between institutions, there is much greater inter-institutional variability in yield for emergency patient CTPA studies. The most surprising result of our study is that, differences in methodology notwithstanding, our ED CTPA positivity rates are higher than all but the aforementioned prospective trials. Only three other studies listed in Table 3 found ED CTPA positivity rates greater than 10 %: two Canadian studies [33, 34] and an American study [31]. Although an ideal CTPA positivity rate has not been established, we agree with previous investigators [17] that a yield of 10 % or less reflects CTPA overuse, where the study becomes a screening rather than a diagnostic test. The reasons why our ED CTPA positivity rates are so much higher than the remaining retrospective studies listed in Table 3, as well as the wider interinstitutional variability in ED CTPA yield, should be investigated further. Of note, the remaining studies listed in Table 3 were conducted in the USA; previous investigators have speculated that decreased CTPA positivity rates in US hospitals reflect physician concern for malpractice litigation [17, 23, 31]. In our subgroup of 913 emergency patients who underwent D-dimer and CTPA testing, the high D-dimer sensitivity
Emerg Radiol Table 3 Summary of CTPA positivity rates in recent studies Study
Country of origin
Year
CTPA positivity rate, emergency patients CTPA positivity rate, inpatientsa
Kline et al. [16]b Stein et al. [32]c Perrier et al. [2]d van Belle et al. [1]e Prologo et al. [19] Hall et al. [15] Corwin et al. [18] Brown et al. [23] Costantino et al. [17] Cervini et al. [34]f Mamlouk et al. [21] Stein et al. [31]e Woo et al. [33] Yin et al. [25] Present study
USA Canada and USA Switzerland and France Netherlands USA USA USA USA USA Canada USA USA Canada USA Canada
2001–2002 2001–2003 2002–2003 2002–2004 2002–2003 2002–2003 and 2005 2003–2005 2003 2004–2005 2004–2005 2004–2006 2006 and 2007 2007 2008–2009 2008–2010
57/671 (8.5 %) 175/773 (22.6 %) 187/505 (37.0 %) 674/2,179 (30.9 %) 20/349 (5.7 %) 55/589 (9.3 %) 159/2,620 (6.1 %) 17/287 (5.9 %) 22/258 (8.5 %) 65/511 (12.7 %) 65/1,022 (6.4 %) 162/1,208 (13.4 %) 124/877 (14.1 %) 74/509 (14.5 %) 27/716 (3.8 %) 252/1,677 (15.0 %)
– – 82/501 (16.4 %) – – – 32/267 (12.0 %) 66/329 (20.1 %) 132/981 (13.5 %) 101/723 (14.0 %) – 317/1,894 (16.7 %)
CTPA computed tomography pulmonary angiogram, PE pulmonary embolism a
Includes both ICU and non-ICU
b
Indeterminate studies were excluded
c
Indeterminate studies were excluded. Twenty-five positive CTPA had a normal composite reference standard, which when taken into account yields a true positivity rate of 150/773 (19.4 %)
d
Indeterminate studies were excluded. The prevalence of PE in the entire study population using a combination of CTPA, ventilation–perfusion (VQ), and conventional angiography was 194/756 (25.7 %). Of these, 232 patients had a negative D-dimer and were not imaged e
The listed positivity rates differ from those published in the original articles because indeterminate studies were excluded, as in the present study
f
Includes indeterminate studies as the distribution between indeterminate ED and INPT CPTA is not reported. Only on-call CTPA studies were reviewed in this study
(97.9 %) and NPV (98.4 %) are comparable to an equally large study, which found a D-dimer sensitivity of 95.0 % and NPVof 99.4 % in 992 emergency patients [18]. However, it is important to consider the prevalence of PE, which if low will elevate the D-dimer NPV and lower the PPV [22, 25]. For example, in our subset of 913 patients, the CTPA positivity rate was 15.6 % and the D-dimer PPV was 19.0 %. In contrast, [18] and [25] found CTPA positivity rates of 2.0 and 0.8 % and D-dimer PPVs of 2.3 and 1.5 %, respectively (among emergency patients with CTPA and D-dimer). Although we usually consider the D-dimer sensitivity most important so as to minimize false negatives, a reasonably high specificity—at least 50 %, as suggested by Kline and Wells [35]—is required to be clinically useful and avoid unnecessary imaging. In the same subset, 182/913 (19.9 %) emergency patients underwent CTPA despite a negative D-dimer, which seems contrary to current PIOPED II recommendations [29]. Similar results are reported or derived from data presented in other studies: 32/151 (21.2 %) [17], 166/992 (16.7 %) [18], 111/591 (18.8 %) [25], and 24/122 (19.7 %) [15]. The reasons for this practice in our study are not clear. Given the low prevalence of PE in this subgroup (1.6 %), it is unlikely that this represents inadvertent D-dimer ordering in otherwise high-risk patients.
Prior studies that assigned the Wells score to imaged emergency patients with negative D-dimers found a significant proportion to be of low/intermediate pretest probability and therefore should not have undergone imaging [17, 24, 25]. There is accumulating evidence regarding the drawbacks of CTPA. A recent commentary in the Archives of Internal Medicine [30] argued that the low yield of CTPA, high prevalence of incidental findings requiring follow-up, reduced accuracy with subsegmental PE, and radiation and contrast exposure indicate that CTPA may have been adopted too rapidly and without consideration of the benefits and risks. However, the overall CTPA benefit-to-risk ratio depends on the PE detection rate [36]. Given the wide variability in emergency patient CTPA yield between institutions (Table 3), as well as the variability in CTPA ordering and positivity rates among individual emergency physicians (Fig. 5), the cost and benefits of CTPA appear institution-specific and depend, at least in part, on the practice habits of referring physicians. These factors should be considered when assessing the overall utility of CTPA. The limitations of our study include its conduction at a single, tertiary care center and reliance on CTPA reports.
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Although patient selection bias was minimized by selecting consecutive patients over a 2-year period, our patient population is not necessarily representative of other hospitals. In addition, the practice habits of our physicians, and perhaps 24-h availability of CTPA, may not be generalizable to other centers. We based the diagnosis of PE on the radiologist's report, and not a second expert reading, to compare the historic positivity rates for various time frames and between thoracic and non-thoracic radiologists. Inter-observer differences in CTPA interpretation, such as reporting variability [37] and diagnosis of subsegmental PE [13, 14], could potentially alter our CTPA positivity rates. However, we expect this effect to be small given our large sample size and that no statistical difference was found between interpreting thoracic and non-thoracic radiologists. In summary, the yield of our emergency patient CTPA is relatively high and in contrast to many recently published studies. Our results and the results of other studies presented herein show that there is considerable variability in the yield of ED CTPA among different institutions (Table 3) and individual emergency physicians (Fig. 5c). While further investigation into the reasons for such variation is warranted, these results serve to reinforce the importance of a strong clinical assessment in the work-up of suspected PE.
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Acknowledgments The authors thank Ranjeeta Mallick, Betty Anne Schwartz, Cheryl Alie, and Amanda Skaff for their assistance with this study. 13. Conflict of interest The authors declare that they have no conflict of interest. 14.
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the Fleischner Society. Radiology 245(2):315–329. doi:10.1148/ radiol.2452070397 Stein PD, Woodard PK, Weg JG, Wakefield TW, Tapson VF, Sostman HD, Sos TA, Quinn DA, Leeper KV Jr, Hull RD, Hales CA, Gottschalk A, Goodman LR, Fowler SE, Buckley JD (2007) Diagnostic pathways in acute pulmonary embolism: recommendations of the PIOPED II Investigators. Radiology 242(1):15–21. doi:10.1148/radiol.2421060971 Schattner A (2009) Computed tomographic pulmonary angiography to diagnose acute pulmonary embolism: the good, the bad, and the ugly: comment on "The prevalence of clinically relevant incidental findings on chest computed tomographic angiograms ordered to diagnose pulmonary embolism". Arch Intern Med 169(21):1966– 1968. doi:10.1001/archinternmed.2009.400 Stein EG, Haramati LB, Chamarthy M, Sprayregen S, Davitt MM, Freeman LM (2010) Success of a safe and simple algorithm to reduce use of CT pulmonary angiography in the emergency department. AJR Am J Roentgenol 194(2):392–397. doi:10.2214/AJR.09.2499 Stein PD, Fowler SE, Goodman LR, Gottschalk A, Hales CA, Hull RD, Leeper KV Jr, Popovich J Jr, Quinn DA, Sos TA, Sostman HD, Tapson VF, Wakefield TW, Weg JG, Woodard PK (2006) Multidetector computed tomography for acute pulmonary embolism. N Engl J Med 354(22):2317–2327. doi:10.1056/NEJMoa052367 Woo JK, Chiu RY, Thakur Y, Mayo JR (2012) Risk-benefit analysis of pulmonary CT angiography in patients with suspected pulmonary embolus. AJR Am J Roentgenol 198(6):1332–1339. doi:10.2214/ AJR.10.6329 Cervini P, Bell CM, Roberts HC, Provost YL, Chung TB, Paul NS (2008) Radiology resident interpretation of on-call CT pulmonary angiograms. Acad Radiol 15(5):556–562. doi:10.1016/j.acra.2007. 12.007 Kline JA, Wells PS (2003) Methodology for a rapid protocol to rule out pulmonary embolism in the emergency department. Ann Emerg Med 42(2):266–275 Araoz PA, Haramati LB, Mayo JR, Barbosa EJ Jr, Rybicki FJ, Colletti PM (2012) Panel discussion: pulmonary embolism imaging and outcomes. AJR Am J Roentgenol 198(6):1313–1319. doi:10. 2214/AJR.11.8461 Abujudeh HH, Kaewlai R, Farsad K, Orr E, Gilman M, Shepard JAO (2009) Computed tomography pulmonary angiography: an assessment of the radiology report. Acad Radiol 16(11):1309–1315
ORIGINAL ARTICLE
The yield of CT pulmonary angiograms to exclude acute pulmonary embolism Andreu F. Costa & Hamed Basseri & Adnan Sheikh & Ian Stiell & Carole Dennie
Received: 27 August 2013 / Accepted: 9 October 2013 # Am Soc Emergency Radiol 2013
Abstract There is accumulating evidence regarding the overuse of computed tomography pulmonary angiography (CTPA) to exclude pulmonary embolism (PE). We evaluated the yield of CTPA studies performed at our tertiary care hospital between April 2008 and March 2010 for emergency patients (ED), inpatients (INPT), and intensive care unit inpatients (ICU). For each patient group, we also compared CTPA positivity rates among the following: daytime and on-call studies, 1 year before and after institution of an Emergency Radiology division, interpreting thoracic and non-thoracic radiologists, and individual emergency physicians. Patients with a history of PE and indeterminate studies were excluded. The diagnosis of PE was based on the radiology report. D-dimer values obtained within 24 h prior to CTPA were recorded. A total of 3,571/4,757 CTPA studies satisfied the inclusion criteria. The fraction of positive studies was 252/1,677 (15.0 %) ED, 255/1,548 (16.5 %) INPT, and 62/346 (17.9 %) ICU. There was no difference in yield between patient groups, daytime vs. on-call studies, before vs. after instituting an emergency radiology division, and thoracic vs. non-thoracic radiologists (p >0.05). For individual emergency physicians, A. F. Costa (*) : A. Sheikh : C. Dennie Department of Medical Imaging, The Ottawa Hospital, Civic Campus, 1053 Carling Avenue, Ottawa, Ontario K1Y 4E9, Canada e-mail: [email protected] A. F. Costa : H. Basseri : A. Sheikh : C. Dennie Department of Radiology, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada I. Stiell Department of Emergency Medicine, The Ottawa Hospital, Ottawa, Ontario, Canada I. Stiell Ottawa Hospital Research Institute, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada
the mean CTPA positivity rate was 15.4 % but varied considerably (σ =8.5 %, range, 0–38.5 %). In comparison to other recent studies, our yield of ED CTPA is relatively high but varied widely among individual emergency physicians. While the reasons for such differences require further investigation, our results reinforce the importance of a strong clinical assessment in the work-up of suspected PE. Keywords Computed tomography pulmonary angiography . Pulmonary embolism . Emergency medicine . D-dimer
Introduction Computed tomography pulmonary angiography (CTPA) is often the first-line imaging test for excluding pulmonary embolism (PE); it is accurate, fast, readily available and provides ancillary findings and alternative diagnoses. Withholding anticoagulation after a negative CTPA is associated with a very low risk of significant venous thromboembolic disease in the near future [1–6]. In most clinical situations, the advantages of CTPA are considered to outweigh the drawbacks of ionizing radiation, use of iodinated contrast, and health care cost. However, recent studies have presented other potential disadvantages of CTPA. These include the overdiagnosis of clinically irrelevant PE [6–10], decreased specificity and interobserver agreement in detecting subsegmental PE [11–14], and a high prevalence of incidental findings requiring clinical or imaging follow-up [15, 16]. Perhaps the most important issue with CTPA is the growing body of evidence regarding its overuse [17–20] and concomitant low yield. Several studies report positivity rates of less than 10 %, raising concerns about whether CTPA is being inappropriately used to exclude PE [15–18, 21–23]. Indeed, studies show that ordering physicians [17, 18, 20, 24, 25] make suboptimal use of validated clinical algorithms to assess for PE, such as the modified Wells criteria [26, 27],
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despite recommendations to the contrary by many expert groups including the Fleischner Society [28] and PIOPED II investigators [29]. The issues surrounding CTPA have led to imaging strategies and arguments [22, 30, 31] against CTPA as a first-line tool for excluding PE. Given the opposing trends of increasing use and decreasing yield, the objectives of this study were to perform a large health record review of CTPA studies performed at our institution over a 2-year period, compare our positivity rates with the literature, and assess for any differences in yield among the following subgroups: emergency patients (ED), inpatients (INPT), and intensive care unit inpatients (ICU), daytime and on-call studies, before and after institution of an Emergency Radiology division, interpreting thoracic and non-thoracic radiologists, and individual referring emergency physicians.
the CTPA study; as in other studies [18, 25], D-dimer values obtained outside this window were disregarded. The D-dimer used at our institution is an automated and fully quantitative, latex-enhanced immunoassay (Instrumentation Laboratory Company, Bedford, MA, USA) and is considered positive when greater than 300 μg/L and negative otherwise. An indeterminate D-dimer result, such as a hemolyzed sample, was considered equivalent to not performing the test if a repeat sample was not obtained. Emergency patients with negative D-dimer and positive CTPA studies were investigated further by obtaining a retrospective Wells score from the electronic health record, as well as the size and location of pulmonary emboli from the CTPA images. CTPA imaging and protocol
Materials and methods Patient data collection This study was Freedom of Information and Protection of Privacy Act (FIPPA) compliant and approved by our research ethics board; as this was a health record study, patient consent was not required. The study was conducted at a large tertiary care, adult teaching hospital in Canada that receives over 124, 000 emergency visits annually. We reviewed all CTPA studies performed on emergency department and admitted patients between April 1, 2008 and March 31, 2010 inclusively. Exclusion criteria were as follows: any non-emergency outpatient study, patients with a history of PE including chronic PE, CTPA studies performed after PE was incidentally diagnosed on another imaging test, any CTPA study not performed to rule out PE (e.g., vascular malformation), and any indeterminate CTPA study. The following characteristics of CTPA studies were obtained from the hospital picture archiving and communication system: patient age and sex, date and timestamp of study, referring physician, reporting radiologist, patient location (emergency, ICU, or non-ICU), and CTPA test result based on the final radiology report (positive, negative, or indeterminate). Note that CTPA studies where segmental or subsegmental PE could not be excluded were still classified as negative or positive, based on the radiologist's impression. Indeterminate studies were classified as such when the study was non-diagnostic or when the radiologist recommended further testing, such as a repeat CTPA, ventilation–perfusion scan, or lower extremity ultrasound. D-dimer Each patient's electronic health record was searched for a serum D-dimer value obtained within 24 h prior to undergoing
CTPA studies varied in protocol and were performed on GE (General Electric Medical Systems, Milwaukee, WI, USA) and Toshiba (Toshiba Medical Systems, Otawara Japan) scanners: GE 64 detector VCT (0.625-mm helical acquisition with 1.25-mm consecutive axial reconstructions), GE LightSpeed 16 (0.625-mm helical acquisition with 1.25-mm axial reconstructions), GE LightSpeed Plus (0.625-mm helical acquisition with 2.5-mm axial reconstructions at 1.25-mm interval), Toshiba Aquilion ONE (0.5-mm helical acquisition with 1.0-mm consecutive axial reconstructions), and Toshiba Aquilion 64 (0.5-mm helical acquisition with 1.0-mm consecutive axial reconstructions). Between 60 and 120 mL of iopamidol (Isovue-370, Bracco Diagnostics Inc., Princeton, NJ, USA) was injected at a rate of 4–5 cm3/s using an automated, computer-controlled device triggered by timing and threshold software. Radiologists Of the 35 interpreting radiologists, 27 were board-certified by the Royal College of Physicians and Surgeons of Canada and/ or the American Board of Radiology. Eight radiologists trained outside North America and worked under an academic license. Two radiologists were not fellowship trained; all others were subspecialized in one of thoracic, abdominopelvic, musculoskeletal, women's imaging, or interventional radiology. We collected data from the April 2008 to March 2010 time frame specifically to assess for any changes before and after institution of an Emergency Radiology division in April 2009. Prior to April 2009, imaging studies at our institution were assigned by radiological subspecialty; as such, CTPA studies were interpreted by thoracic radiologists during routine working hours. The Emergency Radiology division was created to improve wait times and expedite patient care in the Emergency Department; after April 2009, a non-thoracic
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radiologist reported all emergency patient CTPA studies during routine working hours. We obtained a full year of data before and after the Emergency Radiology division started to assess for any changes in CTPA ordering practices and yield, as well as CTPA reporting practices by thoracic vs. nonthoracic radiologists.
of clinical hours worked by each emergency physician over the 2-year study period was obtained. These data were used to normalize the number of CTPA studies ordered by each physician. Physicians who ordered fewer than 10 CTPA studies in the 2-year period were excluded from analysis. Statistical analysis
Patient data analysis Data analysis was performed using MATLAB (R2011a, Natick, MA, USA) and GraphPad Prism (5.00, La Jolla, CA, USA). For all patient data analyses, data were divided into three patient groups: ED, INPT, and ICU. Each patient group was analyzed for the number of positive and negative CTPA acquired during the following periods of interest: (1) the entire study period, April 2008 to March 2010; (2) routine working hours (Monday to Friday, 0800–1700 h) and on call (Monday to Friday, 1700–0800 h, and all day on weekends and holidays); and (3) the first (April 2008 to March 2009) and second (April 2009 to March 2010) years of interest, before and after institution of the Emergency Radiology division. To assess for any trend over time, comparison between the first and second years of CTPA data was also made by performing a linear regression of monthly ordering and positivity rates for each patient group in each year. To assess for any diurnal trend in CTPA ordering, a histogram was made of the CTPA study timestamps for each patient group, binned in 2-h timeslots throughout the day (0800–1000 h, 1000–1200 h, etc.). Radiologist data analysis The number of positive and negative CTPA studies reported by thoracic and non-thoracic radiologists was recorded for each patient group as well as for the entire cohort. Radiologists who interpreted fewer than 10 CTPA studies over the 2-year period were excluded from analysis.
Statistical analysis was performed using GraphPad Prism. The mean ages of each patient group were compared using the one-way analysis of variance (one-way ANOVA), and the variances were compared using Bartlett's test. Statistical comparison between each CTPA characteristic of interest was performed using the chi-square test.
Results A flowchart of included and excluded CTPA studies is presented in Fig. 1; note that only one exclusion criterion is counted per study, although multiple criteria may have applied. A total of 4,757 CTPA studies were performed during the study period; of these, 1,186 were excluded, leaving 3,571 studies. Patient groups A summary of patient and reporting radiologist results for each patient group is provided in Table 1. The number of included ED, INPT, and ICU CTPA studies was 1,677 (47 %), 1,548 (43.3 %), and 346 (9.7 %), respectively. The mean age in years and percentage of females (in parentheses) for each group were 60.4 (56.5 %) ED, 64.9 (55.5 %) INPT, and 61.5 (52.0 %) ICU. The mean ages were significantly different from each other (one-way ANOVA, p 0.05). The only series with a statistically significant non-zero slope was the ED CTPA ordering rate in the second year (p =0.007). Interpreting radiologists Thirty-one radiologists interpreted at least 10 CTPA studies over the 2-year study period. Thoracic radiologists interpreted approximately twice as many INPT and ICU CTPA studies as non-thoracic radiologists: 1,090 vs. 453 for INPT and 229 vs. 116 for ICU. For ED studies, the pattern was generally reversed: 630 vs. 1,045. There was no statistical difference in the number of positive CTPA studies interpreted by thoracic and non-thoracic radiologists for any of the patient groups (p =0.94, 0.55, and 0.77 for ED, INPT, and ICU, respectively), nor for the entire cohort combined (p =0.95).
Table 2 presents the number of positive, negative, and unavailable serum D-dimer values for each patient group according to CTPA result, positive or negative. Although the true performance of D-dimer cannot be assessed from our data because the number of true and false negatives is unknown (most patients with negative D-dimer would not have been evaluated further with CTPA), a subgroup of 913 emergency patients underwent both CTPA and D-dimer testing. In this subgroup, the D-dimer sensitivity was 97.9 % (95 % CI 94.0– 99.6) and the negative and positive predictive values (NPV and PPV) were 98.4 % (95 % CI 95.3–99.7) and 19.0 % (95 % CI 16.2–22.1), respectively. In the same subset, there were 182/913 (19.9 %) emergency patients who underwent CTPA despite a negative D-dimer, and only three of these CTPA studies were positive (1.6 %). Of the three patients with negative D-dimer and positive CTPA, all were of moderate pretest probability and had small PEs in the segmental or subsegmental pulmonary artery branches. Interestingly, each patient had strong risk factors for possible thrombosis: one patient was subsequently diagnosed with heterozygous factor V Leiden thrombophilia, another had a history of long-term immobility at home after being discharged from the hospital for subdural hemorrhage, and the third patient was undergoing chemotherapy for diffuse metastatic colorectal cancer.
Discussion Our results showed no significant difference in the yield of CTPA among emergency patients, inpatients, and ICU patients. Although we found that the annual CTPA positivity
Emerg Radiol Table 2 D-dimer results according to patient location and CTPA test result
ED, positive CTPA ED, negative CTPA INPT, positive CTPA INPT, negative CTPA ICU, positive CTPA ICU, negative CTPA
D-dimer positive
D-dimer negative
D-dimer not acquired
139 (8.3 %) 592 (35.3 %) 41 (2.6 %) 128 (8.3 %) 4 (1.2 %) 23 (6.6 %)
3 (0.2 %) 179 (10.7 %) 1 (0.1 %) 16 (1.0 %) 0 (0 %) 3 (0.9 %)
110 (6.6 %) 654 (39.0 %) 213 (13.8 %) 1,149 (74.2 %) 58 (16.8 %) 258 (74.6 %)
CTPA computed tomography pulmonary angiogram, ED emergency department patient, ICU intensive care unit inpatient, INPT non-ICU inpatient
Fig. 5 In these vertical bar graphs, each bar corresponds to 1 of 44 individual emergency physicians, and the same physician is represented at the same location on the x-axis in parts a, b, and c. a Total number of CTPA studies ordered by each emergency physician over the 2-year study period. b CTPA studies ordered normalized according to thousands of clinical hours worked by each emergency physician. c CTPA positivity rate for each emergency physician, that is, the number of positive CTPA studies divided by the total number of CTPA ordered for each emergency physician. CTPA computed tomography pulmonary angiogram
rate decreased for each patient group following institution of the Emergency Radiology division, these results were also not statistically significant. However, we discovered a substantial drop in positive ED CTPA studies (16.9 vs. 13.6 %, p =0.06) and significantly increasing monthly ED CTPA ordering rates in the second year (Fig. 4). We are currently investigating the
yield of other emergency patient imaging studies, as well as expanding our CTPA database, to assess whether emergency physicians have become more inclined to order imaging tests following institution of the Emergency Radiology division. Our chart review of the yield and characteristics of CTPA imaging is one of the largest and longest-spanning to date. Shown in Table 3 are CTPA positivity rates reported or derived from similar studies performed over the last decade. Interestingly, the highest CTPA positivity rates were found in the US and Canadian PIOPED II study [32], the Dutch Christopher study [1], and a Swiss and French study [2]. These were multicenter, prospective cohort trials that mandated all patients with suspected PE to be evaluated with the Wells, modified Wells, or Geneva criteria, respectively. Therefore, these landmark trials do not reflect actual clinical practice but rather ideal work-up protocol. Table 3 shows that, whereas the yield of inpatient CTPA is generally comparable between institutions, there is much greater inter-institutional variability in yield for emergency patient CTPA studies. The most surprising result of our study is that, differences in methodology notwithstanding, our ED CTPA positivity rates are higher than all but the aforementioned prospective trials. Only three other studies listed in Table 3 found ED CTPA positivity rates greater than 10 %: two Canadian studies [33, 34] and an American study [31]. Although an ideal CTPA positivity rate has not been established, we agree with previous investigators [17] that a yield of 10 % or less reflects CTPA overuse, where the study becomes a screening rather than a diagnostic test. The reasons why our ED CTPA positivity rates are so much higher than the remaining retrospective studies listed in Table 3, as well as the wider interinstitutional variability in ED CTPA yield, should be investigated further. Of note, the remaining studies listed in Table 3 were conducted in the USA; previous investigators have speculated that decreased CTPA positivity rates in US hospitals reflect physician concern for malpractice litigation [17, 23, 31]. In our subgroup of 913 emergency patients who underwent D-dimer and CTPA testing, the high D-dimer sensitivity
Emerg Radiol Table 3 Summary of CTPA positivity rates in recent studies Study
Country of origin
Year
CTPA positivity rate, emergency patients CTPA positivity rate, inpatientsa
Kline et al. [16]b Stein et al. [32]c Perrier et al. [2]d van Belle et al. [1]e Prologo et al. [19] Hall et al. [15] Corwin et al. [18] Brown et al. [23] Costantino et al. [17] Cervini et al. [34]f Mamlouk et al. [21] Stein et al. [31]e Woo et al. [33] Yin et al. [25] Present study
USA Canada and USA Switzerland and France Netherlands USA USA USA USA USA Canada USA USA Canada USA Canada
2001–2002 2001–2003 2002–2003 2002–2004 2002–2003 2002–2003 and 2005 2003–2005 2003 2004–2005 2004–2005 2004–2006 2006 and 2007 2007 2008–2009 2008–2010
57/671 (8.5 %) 175/773 (22.6 %) 187/505 (37.0 %) 674/2,179 (30.9 %) 20/349 (5.7 %) 55/589 (9.3 %) 159/2,620 (6.1 %) 17/287 (5.9 %) 22/258 (8.5 %) 65/511 (12.7 %) 65/1,022 (6.4 %) 162/1,208 (13.4 %) 124/877 (14.1 %) 74/509 (14.5 %) 27/716 (3.8 %) 252/1,677 (15.0 %)
– – 82/501 (16.4 %) – – – 32/267 (12.0 %) 66/329 (20.1 %) 132/981 (13.5 %) 101/723 (14.0 %) – 317/1,894 (16.7 %)
CTPA computed tomography pulmonary angiogram, PE pulmonary embolism a
Includes both ICU and non-ICU
b
Indeterminate studies were excluded
c
Indeterminate studies were excluded. Twenty-five positive CTPA had a normal composite reference standard, which when taken into account yields a true positivity rate of 150/773 (19.4 %)
d
Indeterminate studies were excluded. The prevalence of PE in the entire study population using a combination of CTPA, ventilation–perfusion (VQ), and conventional angiography was 194/756 (25.7 %). Of these, 232 patients had a negative D-dimer and were not imaged e
The listed positivity rates differ from those published in the original articles because indeterminate studies were excluded, as in the present study
f
Includes indeterminate studies as the distribution between indeterminate ED and INPT CPTA is not reported. Only on-call CTPA studies were reviewed in this study
(97.9 %) and NPV (98.4 %) are comparable to an equally large study, which found a D-dimer sensitivity of 95.0 % and NPVof 99.4 % in 992 emergency patients [18]. However, it is important to consider the prevalence of PE, which if low will elevate the D-dimer NPV and lower the PPV [22, 25]. For example, in our subset of 913 patients, the CTPA positivity rate was 15.6 % and the D-dimer PPV was 19.0 %. In contrast, [18] and [25] found CTPA positivity rates of 2.0 and 0.8 % and D-dimer PPVs of 2.3 and 1.5 %, respectively (among emergency patients with CTPA and D-dimer). Although we usually consider the D-dimer sensitivity most important so as to minimize false negatives, a reasonably high specificity—at least 50 %, as suggested by Kline and Wells [35]—is required to be clinically useful and avoid unnecessary imaging. In the same subset, 182/913 (19.9 %) emergency patients underwent CTPA despite a negative D-dimer, which seems contrary to current PIOPED II recommendations [29]. Similar results are reported or derived from data presented in other studies: 32/151 (21.2 %) [17], 166/992 (16.7 %) [18], 111/591 (18.8 %) [25], and 24/122 (19.7 %) [15]. The reasons for this practice in our study are not clear. Given the low prevalence of PE in this subgroup (1.6 %), it is unlikely that this represents inadvertent D-dimer ordering in otherwise high-risk patients.
Prior studies that assigned the Wells score to imaged emergency patients with negative D-dimers found a significant proportion to be of low/intermediate pretest probability and therefore should not have undergone imaging [17, 24, 25]. There is accumulating evidence regarding the drawbacks of CTPA. A recent commentary in the Archives of Internal Medicine [30] argued that the low yield of CTPA, high prevalence of incidental findings requiring follow-up, reduced accuracy with subsegmental PE, and radiation and contrast exposure indicate that CTPA may have been adopted too rapidly and without consideration of the benefits and risks. However, the overall CTPA benefit-to-risk ratio depends on the PE detection rate [36]. Given the wide variability in emergency patient CTPA yield between institutions (Table 3), as well as the variability in CTPA ordering and positivity rates among individual emergency physicians (Fig. 5), the cost and benefits of CTPA appear institution-specific and depend, at least in part, on the practice habits of referring physicians. These factors should be considered when assessing the overall utility of CTPA. The limitations of our study include its conduction at a single, tertiary care center and reliance on CTPA reports.
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Although patient selection bias was minimized by selecting consecutive patients over a 2-year period, our patient population is not necessarily representative of other hospitals. In addition, the practice habits of our physicians, and perhaps 24-h availability of CTPA, may not be generalizable to other centers. We based the diagnosis of PE on the radiologist's report, and not a second expert reading, to compare the historic positivity rates for various time frames and between thoracic and non-thoracic radiologists. Inter-observer differences in CTPA interpretation, such as reporting variability [37] and diagnosis of subsegmental PE [13, 14], could potentially alter our CTPA positivity rates. However, we expect this effect to be small given our large sample size and that no statistical difference was found between interpreting thoracic and non-thoracic radiologists. In summary, the yield of our emergency patient CTPA is relatively high and in contrast to many recently published studies. Our results and the results of other studies presented herein show that there is considerable variability in the yield of ED CTPA among different institutions (Table 3) and individual emergency physicians (Fig. 5c). While further investigation into the reasons for such variation is warranted, these results serve to reinforce the importance of a strong clinical assessment in the work-up of suspected PE.
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Acknowledgments The authors thank Ranjeeta Mallick, Betty Anne Schwartz, Cheryl Alie, and Amanda Skaff for their assistance with this study. 13. Conflict of interest The authors declare that they have no conflict of interest. 14.
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