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Fifteen studies were finally identified for this meta-analysis[10, 16-30]. The flow diagram of search results is summarized in Figure 1. The number of cases ranged from 42 to 1, 005, involving a total of 3, 309 patients. The detailed characteristics of selected studies are showed in Table 1 and Table 2.
Authors Year Patients
(n)Study Country US Operator Study Type Consecutive Time Interval Scanning Protocol Reference Standard Probe Type Pivetta et al.[17] 2015 1, 005 Italy EP Cohort study 2 < 90 min 6 zones Final hospital diagnosis Curvilinear transducer
(3-5 MHz)Russell et al.[18] 2014 99 America EP Observational study 2 < 90 min 8 zones Blinded chart review Curvilinear probe
(3-5 MHz)Mumoli et al.[19] 2015 226 Italy Nurse Observational study 1 < 90 min 8 zones Final hospital diagnosis Curved array transducer
(2-5.5 MHz)Arrgarwal et al.[20] 2016 42 India Cardiologist Cross-sectional study 1 IMR 28 scan sites Blinded chart review Portable machine
(not specified)Prosen et al.[21] 2011 218 Slovenia EP Cohort study 1 < 90 min 8 zones Final hospital diagnosis Not specified Liteplo et al.[10] 2009 94 America EP Observational study 2 > 90 min 8 zones Blinded chart review Curved array transducer
(2-5 MHz)Shah et al.[22] 2016 117 America Internal medicine resident Cohort study 2 NR 8 zones Final hospital diagnosis Phased array transducer Pirozzi et al.[23] 2014 167 Italy EP Observational study 2 < 90 min 8 zones Final hospital diagnosis Convex probe (3.5 MHz)
Cardiac transducer
(2.5-3.5MHz)Kajimoto et al.[24] 2012 90 Japan Cardiologist Observational study 1 < 90 min 8 zones Phased array probe
(l.7-3.5MHz)Sartini et al.[25] 2016 236 Italy EP Observational study 2 > 90 min 12 zones Final hospital diagnosis Convex probe (3.5-5 MHz) Volpicelli et al.[30] 2006 300 Italy EP and radiologist Observational study 1 > 90 min 8 zones Final hospital diagnosis Convex probe (3.5 MHz) Cibinel et al.[26] 2011 56 Italy EP Observational study 2 > 90 min 8 zones Final hospital diagnosis Convex probe (3.5 MHz) Chiem et al.[27] 2015 380 America EM resident Cross-sectional study 2 < 90 min 8 zones Blinded chart review Curvilinear transducer
(2-5 MHz)Li et al.[28] 2016 187 China Sonographer Cohort study 2 > 90 min 28 scan sites Echocardiography with Doppler S5-1 probe (1-5 MHz) Unluer et al.[29] 2014 96 Turkey Nurse Cross-sectional study 2 < 90 min 6 zones Provisional diagnosis at the end of the ED stay Microconvex probe
(3.6 MHz)Note. NR: not reported; 1: yes: 2: no; EP: emergency physician; EM: emergency medicine; Scanning protocol: The different zones of thoracic ultrasonography considered in each study. Table 1. Characteristics of Eligible Studies
Study Setting Age, y (range) Inclusion Pivetta et al.[17] ED 77 (IQR13) acute dyspnea Russell et al.[18] ED 56 ± 13 (22-91) undifferentiated dyspnea Mumoli et al.[19] ED 78.7 ± 12.7 acute dyspnea Arrgarwal et al.[20] ED 64.4 ADHF suspected Prosen et al.[21] Prehospital emergency setting 70.9 ± 11.7 shortness of breath Liteplo et al.[10] ED 74 ± 14 acute dyspnea Shah et al.[22] ED 36 (17-58) undifferentiated dyspnea Pirozzi et al.[23] ED 74.3 ± 4.3 acute dyspnea Kajimoto et al.[24] ED 78.1 ± 8.1 acute dyspnea Sartini et al.[25] ED 79.98 acute dyspnea not related to any trauma Volpicelli et al.[30] ED 68.4 ± 8.4 alveolar-interstitial syndrome suspected Cibinel et al.[26] ED 82.1 (38.7-94.3) acute dyspnea Chiem et al.[27] ED 55 ± 5 dyspnea Li et al.[28] ED 62.4 ± 2.4 acute dyspnea Unluer et al.[29] ED 70.59 acute dyspnea Note. IQR: interquartile range; ADHF: Acute decompensated heart failure; SD: Standard deviation. Table 2. Patient Characteristics
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Figure 2 and Figure 3 show the quality assessment of individual studies.
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The summary sensitivity and specificity values were 0.85 [95% confidence interval (CI), 0.84-0.87], and 0.91 (95% CI, 0.89-0.92) (Figure 4). The summary PLR, NLR, and diagnostic odds ratio (DOR) were 8.94 (95% CI, 5.64-14.18), 0.14 (95% CI, 0.08-0.26) and 67.24 (95% CI, 31.78-142.28). The HSROC was 0.9587 (SE, 0.0130) (Figure 5). The Deeks' funnel plot asymmetry test showed no evidence of significant publication bias (P = 0.783) (Figure 6).
Figure 5. Summary receiver operating characteristic (SROC) curves for the detection of AHF using ULCs.
We detected significant heterogeneity among included studies, and therefore, all these results were analyzed under the random-effect model. Spearman rank correlation was -0.214 (P = 0.443), which indicated no significant threshold effect among individual studies. We also explored possible sources of heterogeneity among the studies by using meta-regression analysis with the following covariates as predictor variables: patient number (e.g., > 100 vs. < 100), study quality, operator (experienced vs. inexperienced), scanning protocol and the time interval between the patient's admission to bedside TLS examination (< 90 min vs. > 90 min). Results suggest that the time interval was closely related to accuracy (relative DOR, 3.56; 95% CI, 1.01-12.51; P = 0.0480).
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According to the definition of PRIDE AHF scores[16], the pretest probabilities of 20%, 45%, and 70% were evaluated in contrast with post-test probabilities based on a 'positive' or 'negative' ultrasound result. The Fagan plot analysis demonstrated that when the pre-test probabilities were 20%, 45%, or 70%, the positive post-test probabilities of AHF were 74%, 90%, or 96%, respectively (Figure 7). Furthermore, ULCs was helpful to reduce the negative post-probability of AHF to as low as 3% and 8% when the pre-probabilities of 'negative' measurement were 20% and 45%. Although the probability of correctly diagnosing AHF based on a 'positive' ULCs results is as high as 96% when the pretest probability was 70%, the diagnosis would be incorrect in 21% of patients whose ULCs results were 'negative' (Figure 8).
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Five studies reported a time interval between the patient's admission to bedside TLS examination > 90 min[10, 25-26, 28, 30], and the pooled sensitivity, specificity, PLR, NLR, and DOR were 0.67 (95% CI, 0.61-0.72), 0.90 (95% CI, 0.87-0.92), 6.42 (95% CI, 4.14-9.95), 0.35 (95% CI, 0.25-0.50), and 20.14 (95% CI, 9.17-44.24), respectively. The HSROC was 0.8924 (SE, 0.0631). Conversely, eight studies reported a time interval between the patient's admission to bedside TLS examination < 90 min[17-19, 21, 23-24, 27, 29], and the pooled sensitivity, specificity, PLR, NLR, and DOR were 0.91 (95% CI, 0.89-0.92), 0.90 (95% CI, 0.89-0.92), 10.13 (95% CI, 4.87-21.08), 0.07 (95% CI, 0.02-0.24), and 127.8 (95% CI, 46.10-354.30), respectively. The HSROC was 0.9712 (SE, 0.0258). The studies with the evaluation time < 90 min have an overall better sensitivity than the others. According to the summary likelihood ratio calculated from included studies reported the time interval < 90 min (Figure 7), we evaluated the pretest probabilities of 20%, 45%, and 70% against the corresponding post-test probabilities based on 'positive' or 'negative' ULCs results. When the pretest probability was only 20%, the accurate diagnosis probability of AHF was up to 76% based on the positive ULCs result, while the probability was only 1% based on the negative ULCs result; when pretest probability was 45%, the accurate diagnosis probability of AHF was up to 91% based on the positive ULCs result, while the probability was 4% based on the negative ULCs result; when pretest probability was 70%, the accurate diagnosis probability of AHF was up to 97% based on the positive ULCs result, while the probability was 10% based on the negative ULCs result.