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CTPA versus V-Q lung scan in pregnant women
pregnant patients is highly debated. The two most used imaging tests for suspected acute PE in the non-pregnant population are computed tomography pulmonary angiography (CTPA) and ventilation-perfusion (V-Q) lung scanning, with CTPA being the imaging test of choice because of its high accuracy, wide availability, and ability to exclude other pathologies.6,7 As is generally the case with V-Q lung scans, the risk of non-diagnostic tests with CTPA is relatively high, in part because of the hemody- namic changes that occur during pregnancy, such as hemodilution and increased heart rate, which make it necessary to have a CTPA protocol specifically designed for pregnant patients. Additionally, elevation of the diaphragm, due to the enlarged uterus, accentuates the interruption of contrast by non-opacified blood from the inferior vena cava and may lead to decreased contrast attenuation in areas of the pulmonary arteries.6 Moreover, both CTPA and V-Q lung scanning involve exposure of the fetus and patients’ breasts to radiation. The lack of high quality management studies comparing both imag- ing tests fuels an ongoing debate in the literature on which of the two options should be preferred.
We set out to perform a systematic review and meta- analysis of published literature to compare the diagnostic efficiency of CTPA versus V-Q lung scans in pregnant patients with suspected acute PE. We also aimed to com- pare the rate of non-diagnostic scan results and radiation exposure for both the mother and fetus.
Methods
Search strategy
For this meta-analysis, we conducted a search for all relevant full publications in PubMed, EMBASE, Web of Science and the Cochrane Library databases. We searched EMBASE, Web of Science and the Cochrane library databases for relevant meet- ing-abstracts as well. The complete search strategy is detailed in Online Supplementary Appendix A.
Selection of studies
Search results were combined and duplicates were removed. Studies were screened for relevance by two independent reviewers (CT and LvdP) following a specific three-step program and applying Covidence software (www.covidence.org). Disagreements were resolved by a third investigator (FK) by majority rule. The first and second steps consisted of title and abstract screening followed by full text screening for the remain- ing articles. The final selection of the studies to include in the meta-analysis was based on assessment of relevance and study quality. The assessment of relevance was based on the following criteria: (i) prospective patient inclusion, (ii) inclusion of consec- utive patients, (iii) reported rate of non-diagnostic test results, and (iv) reported incidence of PE at baseline. The assessment of bias was evaluated in accordance with the PRISMA criteria:8 (i) pre-specified study protocol, (ii) clear description of inclusion and exclusion criteria, (iii) inclusion of consecutive patients, (iv) objective diagnosis of PE, (v) reported losses to follow-up, (vi) clear distinction between pregnant and post-partum patients, and (vii) assessment of the primary endpoints in all patients. Studies were included in the meta-analyses according to the def- inition of each endpoint.
The final step was data extraction. For each included study, we extracted the first author’s name and year of publication, study design (prospective or retrospective), setting of the study
(single- or multicenter), number of patients in the index cohort, the baseline incidence of PE, the duration of follow up, and the predefined study endpoints.
Study outcomes and definitions
We predefined three major study endpoints. The first was the diagnostic efficiency of both imaging tests as expressed by the number of false negative scans. This first outcome required a fol- low up of at least 3 months as well as reporting of the number of diagnosed PE events during this follow up. The second endpoint was the rate of non-diagnostic results with CTPA and V-Q lung scans. For CTPA, scan results were defined non-diagnostic when the radiologist was unable to confirm or exclude the diagnosis of PE, usually because of suboptimal contrast opacification and res- piratory motion artifacts, or the need for an additional imaging test. For V-Q lung scanning, the definition of non-diagnostic results was based on the PIOPED criteria, i.e. intermediate and low probability scan results, since these require an additional diagnostic test to confirm or rule out PE with sufficient certainty. The third endpoint was fetal and maternal radiation exposure due to CTPA and V-Q lung scanning. The CTPA radiation exposure was collected for studies in real-life patients as well as with anthropometric phantom models simulating a gravid woman.
Statistical analysis
The baseline incidence of PE and rate of false negative scans were calculated with corresponding 95% confidence intervals (95% CI). The number of non-diagnostic results from all studies was collected and the rate of non-diagnostic results was calculat- ed using the number of non-diagnostic tests divided by the num- ber of patients in each study. We applied a random effects model according to DerSimonian and Laird for the calculation of the pooled rates of the four study endpoints.9 We predefined that we would not undertake data pooling in case studies for any of the three endpoints because they were not comparable due to extensive differences in study design or imaging protocols, which do not allow for reliable statistics or data pooling. Heterogeneity across the various cohort studies was assessed by calculating the I2 statistic. Heterogeneity was defined as low when I2 was <25%, intermediate when I2 was 25-75% and high when I2 was >75%.10 All analyses were performed in Stata 14.0 (Stata Corp., College Station, TX, USA).
Results
Study selection
The initial search identified 303 records in PubMed, 318 articles in EMBASE, 76 articles in Web of Science, and three articles in the Cochrane Library. After a first screen- ing of titles and abstracts, 565 articles were excluded. A further 78 articles were excluded based on the predefined inclusion criteria (Figure 1): 20 studies did not report the study outcomes of interest, two articles concerned thy- roid function after CTPA, five articles involved surveys about clinical practice, two articles were duplicates, four were guidelines, five were letters to the editor and did not report the outcomes of interest, 37 were review articles and four were irrelevant case reports. Two additional rel- evant articles were identified after reviewing the refer- ences lists of the selected studies. A final 49 evidence- based studies were fully assessed for study quality6,7,11-57 (Table 1): 13 were included in the analysis of false nega-
tive scans7,14-17,20,33,35,37,45,51,53,55 (Table 2), 30 were included in the analysis of non-diagnostic results7,14-17,19-21,23-29,32-37,45,46,49,52-57
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