An appraisal of clinical practice guidelines for the appropriate use of echocardiography for adult infective endocarditis—the timing and mode of assessment (TTE or TEE)

Echocardiography (echo) is the primary imaging modality for infective endocarditis (IE). A positive echo is defined by vegetation or abscess, and new dehiscence of the prosthetic valve is included as a major modified Duke criterion along with positive microorganisms [1]. In addition, echocardiographic examination is also able to show haemodynamic severity of the valve lesion [2]. The appropriate use of echo should be cost-effective, time-efficient and focused on potential associated complications [3, 4]. Timely and accurate guidance should be available for the diagnosis and management of IE. As per a single-center study, a considerable number of transesophageal echocardiography (TEE) exams were rated as inappropriately used for IE [5]. Over the past 15 years, there have been 9 guidelines that cover IE diagnosis and contain evidence-based recommendations on the appropriate use of echo (all published in English, and the latest version of each guideline was considered). However, these guidelines differ in their recommendations on TEE and transthoracic echocardiography (TTE) application in certain clinical scenarios, which can be confusing for clinical decision makers. APPRAISAL OF GUIDELINES FOR RESEARCH & EVALUATION (AGREE) is an instrument for comprehensive guideline evaluation across 6 domains, including scope and purpose, stakeholder involvement, rigor of development, clarity of presentation, applicability and editorial independence. AGREE II, the updated version developed in 2013, updated certain items from the original version [6]. A systematic review of the appropriate use of echo based on critical assessment and the quality comparison of different guidelines was presented to allow clinicians to make better decisions in certain confusing clinical scenarios.

This is the first time that the controversies among recommendations on the appropriate use of echo were evaluated using the AGREE II score of guidelines.

Of the 9 guidelines, the methodology sections of NHAM 2017 and BHRS 2014 indicated that the entire content was compiled based on the AGREE II principle, and both of these guidelines received a score higher than 60% [12, 15]. However, compared with other guidelines that failed to involve certain AGREE II items and thus obtained lower scores, the superior score of NHAM 2017 is largely due to a more general coverage of items rather than a higher grade for each item. The descriptions referring to Item 19 (facilitators and barriers to the application) and Item 20 (the potential resource) in NHAM 2017 were rather perfunctory and lacked in-depth content. Although AGREE II items are recommended during the development of guidelines, comprehensive coverage is just as important as the quality of coverage.

It should also be noted that some studies have shown that exposure to information provided directly by pharmaceutical companies is associated with higher prescribing frequency, higher costs and lower prescribing quality. Therefore, disclosure of potential COI could be necessary [19, 20]. However, it was found that there was no correlation between the proportion of RWI and the AGREE II score involved in the study. This outcome could have been obtained for a variety of reasons, i.e., some guidelines were found to have a high RWI thanks to a more thorough and accomplished disclosure process and less underreporting. For example, ESC has a very detailed COI appendix [14]. In contrast, only NHAM 2017 mentioned that there was no potential COI to disclose and no further detailed relevant content to present. In that case, it cannot be ruled out that the actual RWI proportion of its guideline committee members was concealed and underreported.

Based on the comparison of the recommendations and viewpoints presented by the guidelines, the algorithms for echo use were similar in most cases. Differing recommendations were mainly given on more specific clinical scenarios, and these recommendations were complementary and without conflict. However, there are 2 issues still up for debate.

TTE has been proven to have a sufficient negative predictive value for NVE in patients with low to intermediate risk when strict negative criteria were applied [21, 22]. For these low-risk patients stratified based on clinical judgment with negative TTE, evidence revealed and guidelines proposed that TEE was not necessary [10‐14, 16, 17, 23‐25]. For a first-line negative TTE with undiagnosed but high suspicion of IE, a follow-up TEE is fully agreed upon. However, the maximum time limits given by the guidelines varies from 5 to 10 days (Fig. 4, Table S5). As TEE may fail to detect abnormalities in the early stage, while the severity of pathology distinguished by echo is helpful for the determination of the following management strategy [26], conducting a follow-up TEE within the appropriate time window could be significant. A recent study has shown that an early (< 4 days) definitive echo is associated with fewer embolic events than echos administered later [27]. Therefore, combining the individual characteristics of each patient, a definitive echocardiogram that identifies the pathology of IE should be timely.

For the most controversial issue of whether a subsequent TEE is mandatory in uncomplicated NVE with initial positive TTE, ESC 2015, JCS 2017 and BASC 2011 recommended TEE for all patients except those with isolated right-sided NVE [14, 16, 17], while NHAM 2017, SSID 2007 and AHA 2015 recommended TEE examination only for those with suspected complications [11‐13]. Therefore, for patients (with the exception of those with isolated right-sided NVE) with no or low risk of complications, which are not uncommon in clinical practice, it is unclear whether TEE examination is necessary. On the one hand, TEE is helpful in evaluating the presence of intracardiac complications, offering prognostic information and helping develop treatment plans. On the other hand, if an initial TTE clearly presents vegetation and the probability of complications is low (presented as a small aortic vegetation, mild aortic regurgitation, and normal left ventricular size and function), a subsequent TEE seems to have no incremental value for the treatment strategy [24], which may lead to the overuse of TEE. However, the recommendation that suggested a subsequent TEE after a positive TTE seemed to be less evidence-based and convincing, with a recommendation class of IIa which indicates that weight of evidence and opinion shows usefulness and/or effectiveness, and an evidence level of C which indicates only consensus of opinion. Similarly, the evidence strength of SSID 2007, which explicitly recommended that there was no need to repeat TEE, is C III, which indicates that the evidence supporting the recommendation is weak. Therefore, there is insufficient evidence on this issue, and additional studies with high evidence levels are needed in the future. In addition, isolated right-side NVE was excluded from the adapted population by ESC 2015, JCS 2017 and BASC 2011, which require a subsequent TEE examination as the right-sided structure is located anteriorly and thus closer to the TTE transducer than the transoesophageal transducer, which allows TTE to offer more valuable information. This was also because a subsequent TEE was found to have no additional value for providing new information in isolated right-sided NVE patients [28].

According to AGREE II and compared with guidelines classified as “Recommended with modification”, those guidelines classified as “Strongly recommended” were more rigorously developed, and the recommendations involved in these guidelines were of higher quality. Clinicians can rely on the guideline quality score when evaluating the recommendations for clinical decision making. In addition, it is also expected that updated to the guidelines will lead to better performance in the domain of “stakeholder involvement”. For the most contentious issue, i.e., whether a subsequent TEE is mandatory in uncomplicated NVE with initial positive TTE, related studies are rarely seen. Therefore, more research on this issue, especially studies with high evidence levels, is desired in the future.