It has been the first time that we evaluated controversies among recommendations on the appropriate use of Echo combined with AGREE II score of guidelines.
Among the 9 guidelines, NHAM 2017 and BHRS 2014 mentioned in the methodology of compiling the entire content on the basis of the AGREE II principle, and both of which had received a score of higher than 60%.[12, 15] However, compared with other guidelines which did not manage to involve some certain AGREE II items and as thus got deducted scores, the superior score of NHAM 2017 had largely owed to a more extensive coverage of items rather than a higher grade of each item. The description of some items in NHAM 2017 is rather perfunctory, which is limited to making a mention without any in-depth content, such as item 19 (facilitators and barriers to the application) and item 20 (the potential resource). Although we endorse the use of AGREE II tool to assist in developing guidelines, criticism comes that comprehensive coverage of quantity is just as important as quality.
One more important point to be noted, since studies had disclosed that the exposure to information provided directly by pharmaceutical companies had been found associated with higher prescribing frequency, higher costs, or lower prescribing quality, disclosure of Potential COI could be very necessary[19, 20]. We found no correlation between the proportion of RWI and the AGREE II score in the guidelines we concerned. There is a possibility that some guidelines were found to have a high RWI due to a more thorough and accomplished disclosure process and less underreporting, like ESC that has a very detailed COI appendix[14]. On the contrary, NHAM 2017 only made a mention of no potential conflict of interest to disclose, no further detailed relevant content was presented, for which it cannot be ruled out that the actual RWI proportion of its guideline committee members concealed and underreported.
By comparing recommendations and viewpoints of different guidelines, we found that upon most occasions, the algorithms of echocardiography usage given by these guidelines are roughly the same. Differentiated recommendations are mainly direct at more specific clinical scenarios, which did not conflict with each other but are complementary.
However, there are also a few issues concerning with conflicting views. The first issue relates to the first-line modality of suspected IE. A Cost-effectiveness Analysis found that the initial use of TEE is the optimal diagnostic strategy for most suspected patients[21]. Also, SSID 2007 recommended TEE as the first choice for its cost efficiency and higher sensitivity for vegetations and complications[11] while all of the other guidelines recommended TTE. However, these guidelines recommended TTE for different reasons, among which AHA 2015 proposed that although TEE is the better choice with higher sensitivity, it is not always immediately available (since a patient did not fast for the preceding 6 hours or the medical institution did not have 24-hour TEE service), thus a TTE is recommended to be conducted as soon as possible, nonetheless it remains a suboptimal alternative[13]. In addition, there are other guidelines like JCS 2017 recommended TTE based on its value in evaluation of valve dysfunction and hemodynamics, also in its feature of noninvasive and repeatable[16]. Actually, with the technological progress of echocardiography, TTE was proved to have a sufficient negative predictive value of native valve endocarditis (NVE) in patients with low to intermediate risk when strict negative criteria are applied[22, 23]. And for these low risk patients stratified based on clinical judgment, although few recommendations had been formed, guidelines had addressed in the context or in the algorithm that a repeated TEE is not required[10–14, 16, 17, 24], which have been verified by recently published Meta-analyses[25, 26]. Thus we could agree that the claim of SSID 2007 that TEE is better as well as more cost efficient than TTE as a first-line examination is outdated, since it was published longer and was blamed for citing studies using obsolete echocardiography methods and mixed methodology[27].
For a first-line negative TTE with undiagnosed but high suspicion of IE, a repeated TEE is of full agreement, but the maximum time limit given by different guidelines was varied from 5 to 7 days. As known, the severity of pathology distinguished by echocardiography could help to determine following management strategy[28], and research has shown that early (< 4 days) definitive echocardiography is associated with less embolic events than late[29]. Therefore, time delays to diagnostic Echo should be avoided.
For the issue that whether a subsequent TEE is mandatory in uncomplicated NVE with initial positive TTE. NHAM 2017 presented in the algorithm graph that patients with low predisposing risk and good response to treatment only need repeated TEE as indicated and before discharge, so did SSID 2007, which recommended for no repeated TEE both for diagnosis and management[11, 12]. And NHAM 2017 proposed that only with high predisposing risk or worsening clinical course like prosthetic valve, various coronary heart disease, appearance of new murmur, presence of heart failure would need a subsequent TEE, and so did AHA 2015[12, 13]. As ESC 2015, JCS 2017 and BASC 2011 recommended a subsequent TEE for all positive TTE except isolated right-sided native valve IE to evaluate the presence of intracardiac complications[14, 16, 17]. If an initial TTE presents the vegetation clearly and the probability of complications is low (presented as a small aortic vegetation, mild aortic regurgitation, and normal left ventricular size and function) then a subsequent TEE seems to make no incremental value for the treatment strategy[25], on which occasion the TEE could be overused. A large and extensive vegetations that are more mobile as well as softer could be more associated with the development of complications and embolic events[30]. Nevertheless, we found no official definition of “uncomplicated IE” in all guidelines, and the above content is cited from other studies. Also, with a recommendation class of IIa which indicates that weight of evidence and opinion is in favor of usefulness and/or effectiveness, and an evidence level of C which refers to only consensus of opinion, the recommendations that suggested a subsequent TEE over a positive TTE seem to be less evidence-based and convincing. Similarly, the strength of evidence given by the SSID 2007 that explicitly recommended no need to repeat TEE is also of C III, which manifests that the evidence to support the recommendation for use/intervention is weak and was derived from opinions of respected authorities, based on clinical experience descriptive studies or reports of expert committees. So, we can conclude that neither side has sufficient evidence in this issue, and more researches with high-grade evidence are needed in the future.