Intracardiac versus transesophageal echocardiography for diagnosis of left atrial appendage thrombosis in atrial fibrillation: A meta‐analysis

Abstract Introduction Left atrial appendage (LAA) thrombus in patients with atrial fibrillation is usually detected by transesophageal echocardiography (TEE). Intracardiac echocardiography (ICE) can be a suitable alternative to detect thrombosis. However, the effectiveness of the two methods for detecting LAA thrombus is still unclear, we performed a meta‐analysis that compared ICE versus TEE for LAA thrombosis. Methods We searched PubMed, Cochrane Library, and Embase for published abstracts and manuscripts on June 1, 2020. The analysis was performed using RevMan 5.3, STATA 15, and Meta‐Disc 1.4. Results Eight studies consists of 1108 patients (TEE = 558 vs. ICE = 550) were included. The average sensitivity of ICE and TEE to diagnose LAA thrombus is 1.0 (95% CI: 0.91–1.00) versus 0.68 (95% CI: 0.49–0.83), and specificity of ICE and TEE to diagnosis of LAA thrombus is 1.0 (95% CI: 0.99–1.00) versus 0.98 (95% CI: 0.96–0.99). The AUC of ICE and TEE is 0.9846 (SEAUC = 0.0196) and 0.9655 (SEAUC = 0.0401), and the Q* statistics is 0.9462 (SEQ* = 0.0406) and 0.9127 (SEQ * = 0.0616), respectively. Z test was performed on Q* statistics (Z = 0.45, p > .05). Conclusion The ICE and TEE have similar diagnostic efficacy for LAA thrombosis, but the ICE has higher sensitivity. Compared with TEE, ICE may be more advantages and prospects for clinical application.


| INTRODUCTION
Atrial fibrillation (AF) is the most common arrhythmia, and the proportion increases with age. The proportion of AF is as high as 8% over 75 years of age. 1 The most effective treatment for AF is radiofrequency ablation and cryoablation, but patients need to exclude the left atrium and left atrial appendage (LAA) thrombosis. The main method is to routinely perform transesophageal echocardiography (TEE) before the operation to exclude LAA thrombus.
Intracardiac echocardiography (ICE) has been increasingly applied to probe the structure of the left atrium and LAA. Currently, the two methods are unclear about the real events of detecting LAA thrombus. Therefore, we performed a meta-analysis.

| Search strategy
After searching PubMed, Cochrane Library, and Embase by using keywords: atrial fibrillation, transesophageal echocardiography, Intracardiac echocardiography, and thrombosis from their inception on June 1, 2020. we found that studies only be published in English language.

| Data extractions and quality assessment
Two independent reviewers screened the documents according to the pre-established inclusion and exclusion criteria and including the documents according to the QUADAS-2 (quality assessment of diagnostic accuracy studies-2) evaluation criteria. 2 Carry out the quality assessment, extract data, and cross-check. If opinions are inconsistent, the third researcher will make a joint decision. The extracted data includes basic information, experimental design, and original data (true positives, false positives, true negatives, and false negatives).

| Statistical analysis
1. Using Q test to detect whether there is heterogeneity, and using I2 to estimate the size of the heterogeneity, and then selecting the appropriate statistical analysis model for subsequent meta-analysis 2. We tabulated true positives, false negatives, false positives, and true negatives in patients with LAA thrombus in ICE and TEE. The random-effects model was used to calculate the average sensitivity, specificity, likelihood ratio, and 95% confidence interval (CI) of TEE and ICE respectively. The Mose's constant linear model was used to fit the SROC curve, and the diagnostic odds ratio (DOR), the area under the curve (AUC), and Q * statistics were used to evaluate the accuracy of the diagnostic tests ICE versus TEE in the diagnosis of LAA thrombus. 3,4 We also used the Z test to analyze whether there are differences between the two diagnostic methods. Calculating the Spearman correlation coefficient ρ of true positive rate and false-positive rate, and analyzing whether there is an threshold effect. Once Q statistic does not prove the heterogeneity is not necessary to look for the Spearman correlation coefficient. Deeks linear regression will be used to assess whether the included studies had publication bias. The statistical software for this article is Review Manager 5.3, STATA 15, and Meta-Disc 1.4, p < .05 is considered statistically significant.

| Search results
A total of 368 articles were found, 336 articles were excluded from reading titles and abstracts, and 30 articles were initially included ( Figure 1).
After further reading the full text, we excluded 22 documents that did not meet the inclusion criteria, and finally adopted a total of 8 documents, and recruited 1108 patients (TEE = 558 vs. ICE = 550). 5-12 QUADAS-2 quality graph ( Figures S2 and S3). Individual study data obtained are given in Table 1. The true positive, false positive, false negative, and true negative of ICE and TEE are shown in (Table S2).

| Heterogeneity test
We have applied DOR as the effect size to analyze the heterogeneity of ICE and TEE, respectively. The Q test proves that Cochran-Q is 1.75 and 6.15 respectively. That means heterogeneity between studies is small.
The sensitivity and specificity of the forest plots are shown in  Figure 3 shows the ICE and TEE forest plots The SROC curve of ICE and TEE to diagnose LAA thrombosis is shown in (Figure S6). The AUC of ICE and TEE is 0.9846 (SEAUC = 0.0196) and 0.9655 (SEAUC = 0.0401), and the Q* statistics is 0.9462 (SEQ* = 0.0406) and 0.9127 (SEQ* = 0.0616), respectively. Z test is performed on Q* statistics (Z = 0.45, p > .05), and there is no statistical difference between ICE and TEE.

| Sensitivity analysis
Sensitivity analysis is performed by reducing one article at a time to assess the impact of a study on the meta-analysis. There is no difference in results after excluding each article.

| Publication bias
We used Deeks to evaluate publication bias for included studies, as shown in ( Figure S7). ICE's Deeks linear regression shows that p < .05, and we found publication bias. were detected during surgical left appendage inspection in these cases. Therefore, TEE could lead to false positive diagnosis of LAA thrombus. 14 The merit of TEE is low cost. Less pain would be performed at ablation operation, and ICE would guide other intracardiac procedures, such as LAA occlusion, ventricular premature beat positioning, and ventricular septal ablation. The use of ICE catheter ablation of AF is associated with significant fewer major complications and lower fluoroscopy and radiofrequency time. 15

| LIMITATIONS
The number of cases reported in the relevant literature retrieved literature is not large enough, and more randomized controlled trials are needed to verify the reliability of the results. The incidence of LAA thrombotic events is low, which may impacts the interpretability of the meta-analysis and its ability to detecting differences. Four studies were performed in a retrospective fashion, which might become a limitation of this meta-analysis.