The value of transthoracic echocardiography in the diagnosis of type A aortic dissection: a Meta analysis of prospective study
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摘要:
目的 通过Meta分析方法评估经胸超声心动图对Stanford A型主动脉夹层（AAD）的诊断效能。 方法 运用Meta-disc1.4和Stata16.0对纳入文献的9组数据的真阳性数、假阳性数、真阴性数、假阴性数进行分析，对敏感度、特异性、阳性似然比、阴性似然比、诊断比值比的合并效应值进行估计，通过汇总ROC曲线下面积和Fagan列线图估计经胸超声心动图的诊断准确度。采用单因素Meta回归探索异质性来源，通过Deeks'漏斗图不对称试验检验发表偏倚。 结果 敏感度的合并效应值为0.72（95% CI: 0.67~0.76），特异性的合并效应值为0.96（95% CI: 0.95~0.97），阳性似然比为13.43（95% CI: 7.19~25.07），阴性似然比为0.26（95% CI: 0.16~0.41），诊断比值比高达75.63（95% CI: 26.53~215.57），汇总ROC曲线下面积为0.95 (95% CI: 0.93~0.97)，Fagan图中验后概率由验前的20%提升至84%。敏感度和特异性Q检验结果显示存在异质性（P < 0.01）。Meta回归显示样本量、人群年龄、超声技术、操作人群、超声诊断标准选择、金标准选择并非是异质性来源；进一步分析显示超声阳性标准设置严格和操作人群缺乏经验均使诊断敏感度过低，可能是本文的异质性来源。Deeks'漏斗图显示纳入的9篇文献不存在发表偏倚（P=0.78）。 结论 经胸超声心动图对AAD具有较高的诊断效能，可作为AAD的初步影像学评估手段。亚组分析提示通过调整超声阳性标准设定以及加强操作人员相关培训可能会减少对AAD的漏诊，进一步提高诊断敏感度。 Abstract:Objective Meta-analysis was used to systematically review the diagnostic efficacy of transthoracic echocardiography on type A aortic dissection (AAD). Methods The Meta-disc1.4 and Stata 16.0 software was used to analyze 9 literatures as well as 9 groups of data including true positive, false positive, true negative and false negative values, and estimated the combined effect values of sensitivity, specificity, positive likelihood ratio, negative likelihood ratio and diagnostic odds ratio were estimated. The area under curve of the summary ROC curve and the Fagan nomogram were summarized to estimate the diagnostic accuracy of transthoracic echocardiography. The sources of heterogeneity were analyzed by Meta-regression analysis. Deeks' funnel diagram asymmetry test was used to test publication bias. Results The combined value of sensitivity was 0.72 (95%CI: 0.67-0.76), specificity was 0.96 (95% CI: 0.95-0.97), positive likelihood ratio was 13.43 (95%CI: 7.19-25.07), negative likelihood ratio was 0.26 (95%CI: 0.16-0.41)and the area under curve was 0.95 (95%CI: 0.93-0.97). The post-test probability increased from 20% to 84% in Fagan nomogram, all indicating a high diagnostic accuracy. Sensitivity and specificity Q test were less than 0.01, which indicated some heterogeneity. Meta-regression showed that sample size, age of population, ultrasound technology, operator population, selection of ultrasound diagnostic criteria and selection of gold standard were not the sources of heterogeneity. However, Subgroup analysis showed that the strict setting of ultrasound positive criteria and the lack of experience in the operator population made the diagnostic sensitivity too low, which may be the source of heterogeneity in our study. Deeks' funnel plot showed that there was no publication bias for the 9 included literatures (P=0.78). Conclusion Transthoracic echocardiography has high diagnostic efficacy for AAD and can be used as a preliminary imaging evaluation method for AAD. However, it may be necessary to adjust the setting of ultrasound positive criteria and strengthen the relevant training of operators to reduce the missed diagnosis of AAD and further improve the diagnostic sensitivity. -
图 4 敏感度（A）、特异性（B）、阳性似然比(C)、阴性似然比(D)，诊断比值比(E)合并效应的森林图及汇总ROC曲线（F）
Figure 4. Forest plots of Sensitivity (A), Specificity (B), PLR (C), NLR (D), DOR (E) and SROC curve (F).
表 1 纳入文献基本特征
Table 1. Basic characteristics of the included literature
Author Year Type Country n Average age (year) True positive（n） False positive（n） False negative（n） True negative（n） Operator Doppler Positive criteria * Gold standard ** A. A. Mcleod[16] 1983 Prospective USA 56 58.7 18 2 3 33 1 No 2 2 Jerome E. Granato[17] 1985 Prospective USA 56 60.8 13 5 0 38 1 No 2 2 R. P. Roudaut[18] 1988 Prospective France 673 62 78 2 13 580 2 No 2 2 Francesco Enia[19] 1989 Prospective Italy 46 57.9 11 0 12 23 1 No 3 1 Christoph A. Nienaber[20] 1994 Prospective Germany 35 51 14 3 2 16 1 Yes 2 2 Artur Evangelista[21] 2010 Prospective Spain 128 61 37 9 8 74 1 Yes 1 2 Peiman Nazerian[22] 2014 Prospective Italy 281 67.7 27 14 23 217 2 Yes 2 2 Peiman Nazerian[23] 2019 Prospective Italy 839 62 45 41 40 713 2 Yes 2 2 Yuan Wang[24] 2020 Prospective China 72 52.7 20 0 2 50 2 Yes 1 1 *Ultrasonic positive standard：1=The aortic intimal separation is floating and oscillating in bands or lines of echo；2=The aortic intimal separation is floating and oscillating in bands or lines of echo+ any of the following：Widening diameter of ascending aorta root >42 mm, pericardial effusion/signs of cardiac tamponade, color Doppler indicates aortic regurgitation；3=The aortic intimal separation is floating and oscillating in bands or lines of echo + widening of ascending aorta root, diameter>42 mm + hydropericardium/signs of cardiac tamponade; **Diagnostic gold standard: 1=Diagnosis by imaging only; 2=Diagnosis by multiple methods (image, operation, autopsy, etc). 
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表 2 Meta回归分析
Table 2. Meta-regression analysis
Inclusion factor Relative diagnostic odds ratio (95% CI) P Age 0.95 (0.63-1.43) 0.745 Sample size 1.00 (0.99-1.01) 0.881 Operator 1.34(0.02-94.49) 0.871 Ultrasonic equipment 0.13(0.01-1.27) 0.071 Ultrasonic diagnostic criteria 0.48(0.02-10.49) 0.578 Gold standard 0.47(0.00-44.30) 0.696 literature（3 vs 6） 0.05(0.01-0.20) 0.002
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表 3 敏感度分析
Table 3. Sensitivity analysis
Literature exclusion Sensitivity（95% CI） Specificity（95% CI） A. A. Mcleod 1983 71%（66%-76%） 96%（95%-97%） Jerome E. Granato 1985 71%（66%-76%） 96%（95%-97%） R. P. Roudaut 1988 67%（61%-73%） 94%（93%-95%） Francesco Enia 1989 73%（68%-78%） 96%（95%-97%） Christoph A. Nienaber 1994 71%（66%-76%） 96%（95%-97%） Artur Evangelista 2010 70%（65%-75%） 96%（95%-97%） Peiman Nazerian 2014 75%（70%-79%） 96%（95%-97%） Peiman Nazerian 2019 78%（72%-82%） 97%（95%-98%） Yuan Wang 2020 71%（66%-75%） 96%（95%-97%）
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