Guidelines meet the criteria
A total of 1015 records were searched out during the literature search, from which 1006 records were removed after the review on title, abstract, and the full-text (Figure 1). As the outcome, 9 guidelines reported by 8 host organizations (some of them are joint-work) finally meet the requirements of including criteria: National Heart Association of Malaysia, version 2017 (NHAM 2017); American Heart Association, version 2015 (AHA 2015); European Society of Cardiology, version 2015 (ESC 2015); British Society for Antimicrobial Chemotherapy, British Heart Rhythm Society, version 2014, (BSAC/BHRS 2014); Japanese Circulation Society, version 2017, (JCS 2017); British Society for Antimicrobial Chemotherapy, version 2011 (BSAC 2011); Spanish Society of Infectious Diseases and Clinical Microbiology, version 2015 (SEIMC 2015); CSC 2015; SSID 2007[10-18]. References of the guidelines is shown in Table S3. Guideline identifier, host organization, region, average AGREE II score, COI, number of Echo recommendations and RWI are summarized in Table 1.
Guidelines appraisal by AGREE II
The scores of each guideline are presented in the radar charts (Figure 2) and Table S4. The AGREE II scores of all guidelines are ranging from 36% to 79% with the median of 55%, among them, 4 guidelines (NHAM 2017, AHA 2015, ESC 2015, BSAC/BHRS 2014)[12-15] are rated as “Strongly recommended” with the score higher than 60%, while the others (JCS 2017, BSAC 2011, SEIMC 2015, CSC 2015, SSID 2007)[10, 11, 16-18] are marked with “Recommended with some modifications” with the score from 36% to 55%. No guideline is rated as “Not recommended” with the score lower than 30%. There is no item with the difference between the scores given by the two reviewers greater than 20%.
The focus of Domain1 (scope and purpose) includes the items about the overall goal, the specific health issues contained in the guideline, and its target population. While in contrast with other domains, guidelines’ performance in this domain is uneventful, that is, most of them generally summarized the concerning issues without any further elaboration. NHAM 2017, BSAC/BHRS 2014, BSAC 2011[12, 15, 17] specifically expounded on the items following the AGREE II rules, thus receiving a relatively high score.
The concern of Domain2 (stakeholder involvement) includes that whether the guideline was developed by appropriate stakeholders and whether the views of its intended users was considered. This domain received the lowest average score when two-thirds of the guidelines are not higher than 33%. Only NHAM 2017, BSAC/BHRS 2014, and JCS 2017[12, 15, 16] specified that to which department the clinical guideline should apply for the specialists. In addition, the view of the patients as the target population was only reported by BSAC/BHRS 2014 in the external review, which was not mentioned by the rest of the guidelines of at all.
Domain 3 (rigour of development) is comprised of the processes of evidence synthesizing, the formulation of the recommendations and the procedure for updating. CSC 2015 and SSID 2007[10, 11] reported no information in regard to the selection of evidence, while BSAC/BHRS 2014, JCS 2017 and BSAC 2011[15-17] had only a little description on this subject. Besides, no updated statements or detailed information on external expert review are presented by the guidelines other than AHA 2015, ESC 2015[13, 14] and NHAM 2017. The narrative of methods for formulating the recommendations is relatively clear, therefore, higher scores were given to the items concerned.
Domain 4 (clarity of presentation) involves the clarity of the description and the format of the guideline, of which the average score is the highest of all domains, and the discreteness of scores is the smallest.
Domain 5 (applicability) deal with the practical implementation, efforts for improving uptake, and resource implications. No additional disseminating materials were provided by the guidelines except for NHAM 2017 ESC 2015 and AHA 2015[12-14]. There are few guidelines made mention of the cost implication. Yet the monitoring and auditing criteria was set precisely by all guidelines with the average score higher than 80%.
Domain 6 (editorial independence) pertains to the transparency declarations, including the funding body and competing interests of guideline development group members. Neither clarification on the funding body nor its influence on the content was mentioned by JCS 2017, CSC 2015 and SSID 2007[10, 11, 16]. Besides, no records on the disclosure of potential COI were mentioned by SSID 2007 and CSC 2015. As a result, there is no correlation between RWI and AGGEE II score (Pearson’s correlation r =-0.081 P =0.863) for the rest of the guidelines.
It was found out that more than half of the guidelines (5 out of 9) had received scores less than 60%. According to the independent-sample t-test, t’-test (editorial independence) and Wilcoxon Rank-Sum test (clarify of presentation), the guidelines marked with “recommended with modification” are statistically different from those with “strongly recommended” in the domains of “rigour of development” (P=0.015), “applicability” (P=0.005) and “editorial independence” (P=0.024) (Figure 3). With regards to the specific items, 8 out of 9 guidelines had received the score of zero on the item of “target population”, which indicates that the existing guidelines generally failed to consider the view of a patient during the formulation of recommendations.
Recommendations on appropriate use of Echo
Recommendations for different clinical scenarios were organized and listed in Table S5 (recommendations with controversies) and Table S6 (recommendations without controversies). As shown in the tables, both consensus and controversy are listed, and the consensus outweighs the controversy.
As per the 5 out of 9 guidelines, when a first-line TTE is proved to be non-diagnostic due to its poor echocardiographic window, a further TEE will be recommended considering its higher sensitivity than TTE (class of recommendation: I, level of evidence: B-C).
For patients with suspected IE under a prosthetic heart valve/intracardiac device, TEE is recommended by 5 out of 9 guidelines (class of recommendation: I, level of evidence: B-C). Furthermore, suggestion for patients with implantable cardiac electronic device (ICED) was given by the guideline of BSAC/BHRS 2014, recommending that Echo should be conducted for patients with implantable cardiac electronic device lead infection (LCED-LI), implantable cardiac electronic device associated native or prosthetic valve endocarditis (LCED-IE) and suspected generator pocked infection concurrent ICED-LI or ICED-IE (level of evidence: B-C).
Echo is recommended for patients with S.aureus bacteremia (SAB) by 7 out of 9 guidelines.(class of recommendation: IIa, level of evidence: B-C).
Follow-up Echo (no mode was not specified) was advised by 5 out of 9 guidelines after the onset of a suspected IE (class of recommendation: I, level of evidence: B-C). Among them, ESC 2015 and CSC 2015 further make it clear that the clinical manifestations of a complication include new murmur, embolism, persisting fever, heart failure, abscess, and atrioventricular block[10, 14], while SSID 2007 only counts a new or progressive heart failure as the indication for a repeated Echo.
For patients under medical therapy, 3 out of 9 guidelines recommended follow-up Echo (class of recommendation: I-IIa, level of evidence: B-C). Besides, the recommended follow-up Echo is only for complicated IE in SSID 2007 (strength of evidence: II C) and IE with suspected development of complications in AHA 2015 (strength of evidence: I B). Moreover, SSID 2007 addressed that TEE is not needed for uncomplicated IE and those with good response to treatment (strength of evidence: II C)[11, 13].
An intraoperative Echo examination for IE patients requiring surgery is recommended by 3 out of 9 guidelines (class of recommendation: I, level of evidence: B-C), and brought up with no formal recommendation by BASC 2011. Moreover, BASC/BHRS 2014 mentioned that patients after IECD removal also need follow-up Echo to identify persisting vegetations (level of evidence: C).
At the completion of antibiotic therapy, TEE is recommended by 6 out of 9 guidelines (class of recommendation: I-IIa, level of evidence: C).
The controversial processing steps in different guidelines’ algorithms were shown in Figure 4, and it can be seen that 7 out of 9 guidelines include the recommendation on the first-line modality of suspected IE. Besides, most of the guidelines (6 out of 7) agreed that TTE should be the first choice (class of recommendation: I, level of evidence: B-C) except that SSID 2007 recommended TEE instead (class of recommendation: I, level of evidence: B).
In the case that an initial TEE showed a negative result, as per the recommendation by 6 out of 9 guidelines, a subsequent TEE should be conducted within a given time limit stipulated by different guidelines when suspicion exists without diagnosis of IE (class of recommendation: I, level of evidence: B-C). However, the maximum time limit given by different guidelines varied from 5 to 10 days.
Regarding whether a TEE is needed for suspected IE with a positive TTE, guidelines’ replies are based on varied target population features. For example, BASC 2011 suggested that a positive TTE should be considered as the indication for a subsequent TEE (no formal recommendation formulated). While ESC 2015 and JCS 2015 excluded the unequivocal isolated right-sided native valve IE (class of recommendation: IIa, level of evidence: C)[14, 16]. In the meantime, NHAM 2017 and AHA 2015 advised that TEE was necessary for patients under the concern for complications. NHAM 2017 mentioned that worsening clinical course and high predisposing risk should be included as the indications for TEE (AHA 2015 is with strength of recommendation of I B, and no formal recommendation is formulated in NHAM 2017)[12, 13]. Besides, SSID 2007 and NHAM 2017 recommended not to use a TEE after a positive TTE for the patients with uncomplicated native valve endocarditis (NVE) and low predisposing risk, as well as the patients who have prompt response to treatment (SSID 2007 is with strength of recommendation of IIIc, no formal recommendation is formulated in NHAM 2017)[11, 12].