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• W2015218947 abstract "In the diagnostic management of patients with suspected pulmonary embolism (PE), an algorithm consisting of clinical probability, D-dimer and computed tomography (CT) has been shown to be safe and efficient [1Van Belle A. Buller H.R. Huisman M.V. Huisman P.M. Kaasjager K. Kamphuisen P.W. Kramer M.H. Kruip M.J. Kwakkel-van Erp J.M. Leebeek F.W. Nijkeuter M. Prins M.H. Sohne M. Tick L.W. The Christopher study investigatorsEffectiveness of managing suspected pulmonary embolism using an algorithm combining clinical probability, D-dimer testing, and computed tomography.JAMA. 2006; 295: 172-9Crossref PubMed Scopus (0) Google Scholar]. However, recently, concerns have been raised regarding the risk of cancer after radiation exposure with CT scanning [2Brenner D.J. Hall E.J. Computed tomography – an increasing source of radiation exposure.N Engl J Med. 2007; 357: 2277-84Crossref PubMed Scopus (6564) Google Scholar, 3Einstein A.J. Henzlova M.J. Rajagopalan S. Estimating risk of cancer associated with radiation exposure from 64-slice computed tomography coronary angiography.JAMA. 2007; 298: 317-23Crossref PubMed Scopus (1213) Google Scholar]. The lifetime attributable risk of cancer is considerable for young women, particularly for breast cancer [3Einstein A.J. Henzlova M.J. Rajagopalan S. Estimating risk of cancer associated with radiation exposure from 64-slice computed tomography coronary angiography.JAMA. 2007; 298: 317-23Crossref PubMed Scopus (1213) Google Scholar]. Compared with CT scanning, however, the breast irradiation with a ventilation-perfusion (V/Q) scan is less than 2% [4Cook J.V. Kyriou J. Radiation from CT and perfusion scanning in pregnancy.BMJ. 2005; 331: 350Crossref PubMed Google Scholar, 5Parker M.S. Hui F.K. Camacho M.A. Chung J.K. Broga D.W. Sethi N.N. Female breast radiation exposure during CT pulmonary angiography.AJR Am J Roentgenol. 2005; 185: 1228-33Crossref PubMed Scopus (227) Google Scholar]. Hence, young women might benefit from an alternative diagnostic strategy to avoid CT and the associated radiation to the breasts. Although V/Q scintigraphy is an established diagnostic test in patients with suspected PE, ventilation scintigraphy is expensive and not available daily in many hospitals. Combining perfusion scintigraphy with chest X-ray (X/Q-scan) instead of ventilation scintigraphy would reduce both costs and radiation. However, as in V/Q scintigraphy, the proportions of non-diagnostic test results using an X/Q-scan is still considerable, as shown earlier [6Stein P.D. Terrin M.L. Gottschalk A. Alavi A. Henry J.W. Value of ventilation/perfusion scans versus perfusion scans alone in acute pulmonary embolism.Am J Cardiol. 1992; 69: 1239-41Abstract Full Text PDF PubMed Scopus (94) Google Scholar, 7De Groot M.R. Turkstra F. Van Marwijk K.M. Oostdijk A.H. Van Beek E.J. Buller H.R. Value of chest X-ray combined with perfusion scan versus ventilation/perfusion scan in acute pulmonary embolism.Thromb Haemost. 2000; 83: 412-5Crossref PubMed Scopus (0) Google Scholar]. It should be noted that these studies assessed patients with suspected PE without stratification according to pre-test clinical probability, D-dimer or age. Young women, in whom irradiation from CT scanning is most harmful, will have less co-morbidity compared with elderly patients. Consequently, this may improve the diagnostic yield of an X/Q-scan in this subgroup. We, therefore, investigated the safety and efficiency of a diagnostic strategy consisting of a clinical decision rule (CDR), D-dimer assay, chest X-ray and perfusion scintigraphy in women aged <50 years with suspected PE, in order to reduce the number of CT scans. The strategy was first analyzed retrospectively in a large diagnostic accuracy study (the ANTELOPE study [8Sanson B.J. Lijmer J.G. Mac Gillavry M.R. Turkstra F. Prins M.H. Büller H.R. Comparison of a clinical probability estimate and two clinical models in patients with suspected pulmonary embolism. ANTELOPE-Study Group.Thromb Haemost. 2000; 83: 199-203Crossref PubMed Scopus (102) Google Scholar]) to evaluate how patients were distributed among the various outcome categories and to assess diagnostic accuracy. Because the original scans were not available for re-examination, we validated the strategy in another diagnostic management study (Leventas study: Kamphuisen PW, Rijnders AJM, Jacobs EM, Ullmann EF, unpublished data). The ANTELOPE study was a large multicenter study, performed in six hospitals in the Netherlands, which assessed various diagnostic methods for pulmonary embolism. The Leventas study was a diagnostic management study, performed in the Rijnstate Hospital, Arnhem, the Netherlands, in which a combination of CDR, D-dimer testing and V/Q-scan in consecutive patients with suspected pulmonary embolism was assessed. Predefined exclusion criteria were the same in both studies [8Sanson B.J. Lijmer J.G. Mac Gillavry M.R. Turkstra F. Prins M.H. Büller H.R. Comparison of a clinical probability estimate and two clinical models in patients with suspected pulmonary embolism. ANTELOPE-Study Group.Thromb Haemost. 2000; 83: 199-203Crossref PubMed Scopus (102) Google Scholar]. Upon referral, clinical probability according to Wells was assessed [9Wells P.S. Anderson D.R. Rodger M. Ginsberg J.S. Kearon C. Gent M. Turpie A.G. Bormanis J. Weitz J. Chamberlain M. Bowie D. Barnes D. Hirsh J. Derivation of a simple clinical model to categorize patients probability of pulmonary embolism: increasing the models utility with the SimpliRED D-dimer.Thromb Haemost. 2000; 83: 416-20Crossref PubMed Google Scholar]. Next, a rapid whole blood D-dimer test or enzyme-linked immunosorbent assay were used in the first and second cohort, respectively. The D-dimer was normal when below 500 μg L−1. V/Q or pulmonary angiography, which were performed and interpreted according to previously described criteria [8Sanson B.J. Lijmer J.G. Mac Gillavry M.R. Turkstra F. Prins M.H. Büller H.R. Comparison of a clinical probability estimate and two clinical models in patients with suspected pulmonary embolism. ANTELOPE-Study Group.Thromb Haemost. 2000; 83: 199-203Crossref PubMed Scopus (102) Google Scholar, 10Hull R.D. Hirsh J. Carter C.J. Raskob G.E. Gill G.J. Jay R.M. Leclerc J.R. David M. Coates G. Diagnostic value of ventilation-perfusion lung scanning in patients with suspected pulmonary embolism.Chest. 1985; 88: 819-28Abstract Full Text Full Text PDF PubMed Google Scholar, 11Van Beek E.J. Reekers J.A. Batchelor D.A. Brandjes D.P. Buller H.R. Feasibility, safety and clinical utility of angiography in patients with suspected pulmonary embolism.Eur Radiol. 1996; 6: 415-9Crossref PubMed Google Scholar], were the reference standard in both cohorts. PE was regarded absent in patients with an unlikely CDR (Wells score ≤4) and a normal D-dimer test [1Van Belle A. Buller H.R. Huisman M.V. Huisman P.M. Kaasjager K. Kamphuisen P.W. Kramer M.H. Kruip M.J. Kwakkel-van Erp J.M. Leebeek F.W. Nijkeuter M. Prins M.H. Sohne M. Tick L.W. The Christopher study investigatorsEffectiveness of managing suspected pulmonary embolism using an algorithm combining clinical probability, D-dimer testing, and computed tomography.JAMA. 2006; 295: 172-9Crossref PubMed Scopus (0) Google Scholar]. In patients with a likely CDR or abnormal D-dimer, a normal perfusion scan ruled out PE. In case of abnormalities on the perfusion scan, the findings were combined with the result of the chest X-ray (X/Q-scan, see Table 1). Perfusion scans with at least one segmental defect and a normal chest X-ray were defined as high probability scans for PE. In all other cases (i.e. defects smaller than segmental or segmental defects but locally abnormal chest X-ray) the X/Q-scan was considered non-diagnostic. These patients would, in theory, require additional testing.Table 1X/Q criteriaANTELOPELeventasNormal Q-scanNormal perfusion scanNormal perfusion scan Near normal perfusion scan: – Small irregularities – Perfusion defects smaller or equal in size and shape to the following chest X-ray abnormalities: Cardiomegaly, enlarged aorta, hila and mediastinum, elevated diaphragm, blunting of the costophrenic angle, pleural thickening, intrafissural collection of liquidHigh probability X/Q-scan≥1 segmental defect and a normal chest X-ray≥1 segmental defect and a locally normal chest X-rayNon-diagnostic X/Q-scanAll other casesAll other cases Open table in a new tab In the ANTELOPE cohort, the outcome of the perfusion scan and chest X-ray were used according to the reports and as documented in the database. The abnormalities on chest X-ray had not been specified to location; therefore, in case of an abnormal Q scan and an ‘abnormal’ chest X-ray, the X/Q-scan was classified as non-diagnostic. In the Leventas cohort, two experienced nuclear medicine physicians blinded to outcome separately re-evaluated the perfusion scans of all women <50 years with a likely CDR or an abnormal D-dimer test, to calculate more accurately predictive values of the X/Q-scan. In case of any abnormalities, the scans were compared ‘locally’ with the chest X-ray for a matched or mismatched abnormality. Disagreement between the two readers was solved by consensus reading. The proportion of patients in each X/Q category was calculated, as well as the positive and negative predictive values, with 95% confidence intervals (CI). The positive predictive value (PPV) was defined as the proportion of patients with a high probability X/Q-scan, who had PE as defined by the reference standard. The negative predictive value (NPV) was defined as the proportion of patients with a normal perfusion scan, who did not have PE according to the reference standard. In the ANTELOPE study, of a total of 517 consecutive patients with a clinical suspicion of PE [8Sanson B.J. Lijmer J.G. Mac Gillavry M.R. Turkstra F. Prins M.H. Büller H.R. Comparison of a clinical probability estimate and two clinical models in patients with suspected pulmonary embolism. ANTELOPE-Study Group.Thromb Haemost. 2000; 83: 199-203Crossref PubMed Scopus (102) Google Scholar], 165 (32%) were women aged <50 years. The D-dimer result was missing in six women, leaving 159 women for analysis. Of these 159 women, 32 (20%) were diagnosed with PE, based on pulmonary angiography in nine women and by high probability V/Q-scan in 23 women. Eighty-one women (51%) had an unlikely CDR and a normal D-dimer test (of whom six had PE). Of the remaining 78 women, 34 (44%; 95% CI, 33–55%) had a normal perfusion scan. The perfusion scintigraphy result was missing in two women. Of the 42 women (54%) with an abnormal perfusion scan, 11 (14%; 95%CI, 8–24%) were categorized as high probability X/Q and 31 (40%; CI, 30–51%) as non-diagnostic X/Q. The PPV and NPV of the X/Q-scan were 82% (CI 52–95%) and 97% (CI 85–99.5%), respectively. The proportion of women with a non-diagnostic test result was 31/159 (19%) based on the total cohort, and 31/78 (40%) in women with a likely CDR or abnormal D-dimer test. Theoretically, CT would be avoidable in 60% of women requiring an imaging test. In the Leventas cohort, 228 patients with clinically suspected PE were included, of whom 78 were women aged <50 years. The reference standard was missing in one woman, leaving 77 patients for this analysis. The prevalence of PE was 19% (15/77). PE was confirmed by pulmonary angiography in three and by high probability V/Q-scan in 12 women. In this cohort, 25 women (32%; 95% CI, 23–44%) had an unlikely CDR and a normal D-dimer test. Thirty of the 52 patients with a likely CDR or abnormal D-dimer had a normal perfusion scan (58%; 95% CI, 44–70%). Thirteen women (25%; CI, 15–38%) had a high probability X/Q-scan; nine women (17%; CI, 9–30%) had an X/Q-scan classified as non-diagnostic. The NPV and PPV were 100% (CI, 89–100%) and 100% (CI, 77–100%), respectively. The proportion of women with a non-diagnostic test result was 9/77 (12%) of the total cohort and 9/52 (17%) of the women with a likely CDR or abnormal D-dimer test. Hence, CT would be avoidable in 83% (CI 70–91%) of women requiring an imaging test. The kappa statistic of agreement between the two readers was 0.92. Our findings indicate that an alternative diagnostic strategy that consists of perfusion scintigraphy combined with chest X-ray appears to be promising to reduce CT scanning in young women. One-third of the patients in both cohorts were women aged less than 50 years: the subgroup of patients who are most vulnerable to the adverse effects of radiation from CT scanning. In 129 young women with suspected PE with either a likely CDR or abnormal D-dimer, the X/Q-scan reliably categorized segmental perfusion defects as non-high or high probability for the presence of PE. Concerning the accuracy of the X/Q-scan, our findings are in agreement with two previous studies which reported a PPV of a high probability scan of 86% when compared with the V/Q-scan [7De Groot M.R. Turkstra F. Van Marwijk K.M. Oostdijk A.H. Van Beek E.J. Buller H.R. Value of chest X-ray combined with perfusion scan versus ventilation/perfusion scan in acute pulmonary embolism.Thromb Haemost. 2000; 83: 412-5Crossref PubMed Scopus (0) Google Scholar] and 93% when compared with pulmonary angiography [6Stein P.D. Terrin M.L. Gottschalk A. Alavi A. Henry J.W. Value of ventilation/perfusion scans versus perfusion scans alone in acute pulmonary embolism.Am J Cardiol. 1992; 69: 1239-41Abstract Full Text PDF PubMed Scopus (94) Google Scholar]. However, the proportion of non-diagnostic test results was only 17% when chest X-ray and Q scan were matched locally, whereas this was 40% and 49% in the previous studies [6Stein P.D. Terrin M.L. Gottschalk A. Alavi A. Henry J.W. Value of ventilation/perfusion scans versus perfusion scans alone in acute pulmonary embolism.Am J Cardiol. 1992; 69: 1239-41Abstract Full Text PDF PubMed Scopus (94) Google Scholar, 7De Groot M.R. Turkstra F. Van Marwijk K.M. Oostdijk A.H. Van Beek E.J. Buller H.R. Value of chest X-ray combined with perfusion scan versus ventilation/perfusion scan in acute pulmonary embolism.Thromb Haemost. 2000; 83: 412-5Crossref PubMed Scopus (0) Google Scholar]. This difference is probably as a result of the younger age of the patients, who have less co-morbidity compared to older patients. According to our results, CT scan could theoretically be avoided in 60% in the first cohort and 83% in the second cohort. Analyses were based on retrospective data, in a small population of young women. Although the 95% confidence intervals were wide, the point estimate PPV was high, especially in the second cohort. Further prospective research is necessary to confirm our findings. Further, the X/Q findings could not be compared with CT, nowadays regarded as the gold standard. However, even with a PPV of 85–90% compared with pulmonary angiography, a high probability V/Q-scan is widely accepted for the presence of PE and justifies anticoagulant treatment [12PIOPEDValue 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: 2753-9Crossref PubMed Google Scholar]. The accuracy of a normal perfusion scan is also well accepted [13Hull R.D. Raskob G.E. Coates G. Panju A.A. Clinical validity of a normal perfusion lung scan in patients with suspected pulmonary embolism.Chest. 1990; 97: 23-6Abstract Full Text Full Text PDF PubMed Google Scholar, 14Kipper M.S. Moser K.M. Kortman K.E. Ashburn W.L. Longterm follow-up of patients with suspected pulmonary embolism and a normal lung scan. Perfusion scans in embolic suspects.Chest. 1982; 82: 411-5Abstract Full Text Full Text PDF PubMed Google Scholar]. Replacing a CT scan for perfusion scintigraphy as a first imaging test to exclude or diagnose PE in young women means less radiation and as a result a lower risk of developing cancer. Our study suggests that a strategy consisting of clinical decision rule, D-dimer testing, perfusion scintigraphy and chest X-ray may reliably exclude or diagnose PE. The authors state that they have no conflict of interest. We gratefully acknowledge B. Hendrickx, Nuclear Physician, Rijnstate Hospital, Arnhem, the Netherlands, for the evaluation of the perfusion scans and chest X-rays." @default.
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• W2015218947 title "An alternative diagnostic strategy in young women with suspected pulmonary embolism" @default.
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