Clinical presentation, microbiology, and prognostic factors of prosthetic valve endocarditis. Lessons learned from a large prospective registry

Antonio Ramos-Martínez; Fernando Domínguez; Patricia Muñoz; Mercedes Marín; Álvaro Pedraz; Mª Carmen Fariñas; Valentín Tascón; Arístides de Alarcón; Raquel Rodríguez-García; José María Miró; Josune Goikoetxea; Guillermo Ojeda-Burgos; Francesc Escrihuela-Vidal; Jorge Calderón-Parra; On behalf of the GAMES investigators

doi:10.1371/journal.pone.0290998

Peer Review History

Original SubmissionJune 14, 2023
6 Jul 2023 Decision Letter - Redoy Ranjan, Editor PONE-D-23-16421Clinical presentation, microbiology, and prognostic factors of prosthetic valve endocarditis. Lessons learned from a large prospective registry.PLOS ONE Dear Dr. Ramos-Martínez, Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process. Please submit your revised manuscript by Aug 20 2023 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file. Please include the following items when submitting your revised manuscript: A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'. A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'. An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'. If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter. If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols. We look forward to receiving your revised manuscript. Kind regards, Redoy Ranjan, MBBS, MRCSEd, Ch.M., MS (CV&TS), FACS Academic Editor PLOS ONE Journal Requirements: When submitting your revision, we need you to address these additional requirements. 1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf 2. Thank you for stating the following in the Competing Interests section: "Dr. Ojeda-Burgos has received grants for assistance to medical meetings from Pfizer, Merck Sharp & Dohme, Gilead, Janssen, and Angelini; and has been paid as a speaker in medical meetings from Janssen, Gilead, and Merck Sharp & Dohme. Dr. Miró has received consulting honoraria and/or research grants from Angelini, Bristol-Myers Squibb, Contrafect, Genentech, Gilead Sciences, Merck Sharp and Dohme, Medtronic, Novartis, Pfizer, and ViiV. All authors (including Dr. Ojeda-Burgos and Dr. Miró) have reported that they have no interest conflicts to disclose related to the contents of this paper." Please confirm that this does not alter your adherence to all PLOS ONE policies on sharing data and materials, by including the following statement: "This does not alter our adherence to PLOS ONE policies on sharing data and materials.” (as detailed online in our guide for authors http://journals.plos.org/plosone/s/competing-interests). If there are restrictions on sharing of data and/or materials, please state these. Please note that we cannot proceed with consideration of your article until this information has been declared. Please include your updated Competing Interests statement in your cover letter; we will change the online submission form on your behalf. 3. One of the noted authors is a group or consortium [GAMES investigators]. In addition to naming the author group, please list the individual authors and affiliations within this group in the acknowledgments section of your manuscript. Please also indicate clearly a lead author for this group along with a contact email address. 4. Please include captions for your Supporting Information files at the end of your manuscript, and update any in-text citations to match accordingly. Please see our Supporting Information guidelines for more information: http://journals.plos.org/plosone/s/supporting-information. [Note: HTML markup is below. Please do not edit.] Reviewers' comments: Reviewer's Responses to Questions Comments to the Author 1. Is the manuscript technically sound, and do the data support the conclusions? The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. Reviewer #1: Yes Reviewer #2: Yes ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: Yes ****** 3. Have the authors made all data underlying the findings in their manuscript fully available? The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified. Reviewer #1: Yes Reviewer #2: Yes ****** 4. Is the manuscript presented in an intelligible fashion and written in standard English? PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here. Reviewer #1: No Reviewer #2: Yes ****** 5. Review Comments to the Author Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters) Reviewer #1: Dear the authors. Of the manuscript entitled. Clinical presentation, microbiology, and prognostic factors for prosthetic valve endocarditis. Lessons learned from a large perspective registry. Thank you for writing this manuscript which elaborated on different aspects of Prosthetic Valve Endocarditis Presentation, Microbiology and Prognostic factors. Through a study that included two periods of time. My points to consider. Are the following. 1. This manuscript needs intense English language spelling check. And this language issue is apparently present in almost all of the manuscript sections. 2. There are certain terms that need to be really refashioned such as: Injecting drug user In Table 1., Cardiac insufficiency In Table 2. These terms probably should be rewritten in a more professional way. 3. There was a conflicting sentence to mein the result section in Page. 14. Which says that: Comorbidities, Intracardiac complications and septic shock were more frequent in patients treated during the second period of the study While mortality was improved in this period. This result need to be further explained why mortality was less, despite higher complications and comorbidities were there. 4. The authors mentioned that almost 1/3 of the surgically indicated cases who are having a clear indication for surgery were not operated upon. And these cases that were not operated upon had more risk for mortality. Can you elaborate more? Why there was an obvious reluctance to operate on these patients? And was this a trend because of the surgical risk or the surgeons are hesitant to perform these procedures? 5. Can the authors elaborate more about the methods of echocardiographic assessment used in PVE and whether there was any change between the 2 periods of time 6. The conclusion statement need to reflect the authors opinion about the results they get in this study and should be easy to be understood by the reader. Thank you Reviewer #2: This is a large prospective cohort study in which the authors evaluated the clinical presentation, the microbiology and the prognostic factors of 1354 patients affected of prosthetic valve endocarditis. The authors analysed the data of all patients affected of prosthetic valve endocarditis undergoing and not undergoing a surgical treatment. They excluded correctly the endocarditis on native valve, on pacemaker or ICD and on TAVR. A lot of factors were evaluated and analysed to better understand the characteristics of this population: the survival, the surgical treatment, the time of onset (early or late), the site of prosthetic infection (aortic or mitral) and the study period (2008-2013 or 2014-2020). Moreover, a multivariate analysis of clinical factors associated with in-hospital mortality (with considering and without considering septic shock) were performed. The authors paid particular attention, in the discussion and in the conclusion, to the higher mortality of patients with prosthetic valve endocarditis that presented clear surgical indication and that didn’t undergo cardiac surgery for the higher surgical risk. The topic of this study is very interesting and has been extensively analysed. However, there are some points of discussion: 1. The manuscript needs an English revision. 2. I suggest to add in the Table 1 a column with the characteristics of the “Overall population” of patients affected of endocarditis. This could be interesting considering the high number of patients analysed. 3. In the Figure 1, I suggest to remake the graphic designer in order to better understand the patients included and excluded in the analysis. 4. The lines 205-206, namely the description and the final number of patients analysed in the study, should be moved to the “Patients” section. ****** 6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files. If you choose “no”, your identity will remain anonymous but your review may still be made public. Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy. Reviewer #1: Yes: Salah Eldien Altarabsheh Reviewer #2: No ******** [NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.] While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step. https://doi.org/10.1371/journal.pone.0290998.r001
Revision 1
3 Aug 2023 Author Response Dr. Antonio Ramos Infectious Diseases Unit HU Puerta de Hierro Majadahonda. Madrid. Spain. 28222 29th July 2023 Phone: +34-689 999 333 E-mail: aramos220@gmail.com Dear Editor We would first thank the editor and reviewers for their valuable comments, which have made a substantial contribution to improving the quality of the manuscript: "Clinical presentation, microbiology, and prognostic factors of prosthetic valve endocarditis. Lessons learned from a large prospective registry" [PONE-D-23-16421. In the following lines we will try to respond, to the best of our ability, to each of the referees' recommendations. We hope that the answers provided and the changes made to the manuscript will meet with the approval of the editor and reviewers. Comments to the Author Reviewer #1: 1. This manuscript needs intense English language spelling check. And this language issue is apparently present in almost all of the manuscript sections. A revision of the English language has been carried out in order to improve grammatical correctness and text comprehension. 2. There are certain terms that need to be really refashioned such as: Injecting drug user In Table 1., Cardiac insufficiency In Table 2. These terms probably should be rewritten in a more professional way. We appreciate the reviewer's suggestion. The tables have been revised so that the above and other variables are more appropriately expressed. Reviewing the number of articles that included the different ways of expressing this harmful habit: People Who Inject Drugs, Injecting Drug Users, intravenous Drug Users, we have observed that the last one is the most preferred by the authors. Consequently, we have changed it. Due to the same reason acute renal injury has been replaced by acute renal failure. We have also changed cardiac insufficiency referring to comorbidity for chronic heart failure and heart failure (during hospital admission) for acute heart failure. 3. There was a conflicting sentence to main the result section in Page. 14. Which says that: Comorbidities, Intracardiac complications and septic shock were more frequent in patients treated during the second period of the study While mortality was improved in this period. This result needs to be further explained why mortality was less, despite higher complications and comorbidities were there. In “Discussion” it is mentioned that the better prognosis of the patients in the second period (in spite of presenting a poor clinical situation in some aspects) could be related to a progressive increase in the quality of the medical care provided to the patients over time. The speed of diagnosis, the better visualization of each patient's pathology and the progressive learning of surgical skills in each participating hospital over time are variables that are not easy to ascertain and are probably some of the causes of this finding. To a great degree, we do not know if there is any underlying cause responsible for this prognostic improvement. The discussion has been modified and a bibliographic citation has been added describing a lower mortality over time in patients with PVD. [Perrotta S, Jeppsson A, Fröjd V, Svensson G. Surgical Treatment of Aortic Prosthetic Valve Endocarditis: A 20-Year Single-Center Experience. Ann Thorac Surg. 2016 Apr;101(4):1426-32] . 4. The authors mentioned that almost 1/3 of the surgically indicated cases who are having a clear indication for surgery were not operated upon. And these cases that were not operated upon had more risk for mortality. Can you elaborate more? Table 5 shows a comparison of several variables that allow visualizing the differences between these two groups of patients. Why there was an obvious reluctance to operate on these patients?And was this a trend because of the surgical risk or the surgeons are hesitant to perform these procedures? Failure to perform surgery in patients with an indication is a very relevant problem, but unfortunately it is quite frequent one. We think that there is not a single reason for this fact, but several of them. Advanced age, important comorbidity, the poor prognosis some patients (despite surgery) due to a bad clinical condition of and the degree of experience and professional competence of the different surgical teams are factors related to this problem. We think that in most cases it was assumed that when surgery is rejected, it would not be of any benefit to the patients because of, for example, septic shock or neurological complications. In "Results" the reasons given for not having performed surgery in patients with a surgical indication are shown. In the "Discussion" section we have tried to go deeper into this problem suggesting possible strategies to reduce the number of patients denied surgery. Several comments are presented in relation to the comparison of the clinical characteristics of the patients accepted and rejected for surgery. 5. Can the authors elaborate more about the methods of echocardiographic assessment used in PVE and whether there was any change between the 2 periods of time We are grateful for the reviewer's suggestion. We have added to Table 3S the number of patients in each period in whom transthoracic echocardiography (TTE) and transesophageal echocardiography (TEE) were performed and the number of patients in whom each of these two imaging tests was the only echocardiography performed. There were more cases of patients with TEE performed in the second period. The model of echograph used was not specifically recorded in the database, but the resolution of these technologies, logically, may have progressively improved during the study, although it is not possible to pinpoint the specific changes given the large number of participating hospitals. 6. The conclusion statement need to reflect the authors opinion about the results they get in this study and should be easy to be understood by the reader. We have tried to reflect the authors' opinion on the results in the conclusions section by modifying its structure. We have also tried to improve the reader's understanding. Reviewer #2: This is a large prospective cohort study in which the authors evaluated the clinical presentation, the microbiology and the prognostic factors of 1354 patients affected of prosthetic valve endocarditis. The authors analysed the data of all patients affected of prosthetic valve endocarditis undergoing and not undergoing a surgical treatment. They excluded correctly the endocarditis on native valve, on pacemaker or ICD and on TAVR. A lot of factors were evaluated and analysed to better understand the characteristics of this population: the survival, the surgical treatment, the time of onset (early or late), the site of prosthetic infection (aortic or mitral) and the study period (2008-2013 or 2014-2020). Moreover, a multivariate analysis of clinical factors associated with in-hospital mortality (with considering and without considering septic shock) were performed. The authors paid particular attention, in the discussion and in the conclusion, to the higher mortality of patients with prosthetic valve endocarditis that presented clear surgical indication and that didn’t undergo cardiac surgery for the higher surgical risk. The topic of this study is very interesting and has been extensively analysed. However, there are some points of discussion: 1. The manuscript needs an English revision. A revision of the English language has been carried out to try to improve its grammatical correction. 2. I suggest to add in the Table 1 a column with the characteristics of the “Overall population” of patients affected of endocarditis. This could be interesting considering the high number of patients analysed. A column has been added with the total number of patients as suggested by the reviewer. 3. In the Figure 1, I suggest to remake the graphic designer in order to better understand the patients included and excluded in the analysis. Figure 1 has been modified for a better understanding of the patients included and excluded in the analysis. 4. The lines 205-206, namely the description and the final number of patients analysed in the study, should be moved to the “Patients” section. We agree with the reviewer that this information could be added to "Methods". However, and given that the results include a comparison of patients with IE on native valve with patients with IE on prosthetic valve, we consider that it might be more appropriate to keep under "Results" the total number of patients with IE and the number of patients with each type of infection (native or prosthetic). We would like to thank you once again. Sincerely yours Antonio Ramos Attachments Attachment Submitted filename: Answer to referees.docx https://doi.org/10.1371/journal.pone.0290998.r002
21 Aug 2023 Decision Letter - Redoy Ranjan, Editor Clinical presentation, microbiology, and prognostic factors of prosthetic valve endocarditis. Lessons learned from a large prospective registry. PONE-D-23-16421R1 Dear Dr. Ramos-Martínez, We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements. Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication. An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org. If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org. Kind regards, Redoy Ranjan, MBBS, MRCSEd, Ch.M., MS (CV&TS), FACS Academic Editor PLOS ONE Additional Editor Comments (optional): The authors are thanked for this submission to PLOS ONE. After a critical external peer review by two experts and considering the overall reviewers' comments and authors' responses, your manuscript meets PLOS ONE's publication criteria; fulfils the methodological rigour and ethical standards. Review Comments to the Author Reviewer #1: Dear the authors Thank you for taking in consideration all the reviewers comments I am satisfied with the current version of the manuscript Reviewer #2: Thank you for addressing my comments and for the opportunity to review this paper. There are no further comments from my side. ********** https://doi.org/10.1371/journal.pone.0290998.r003
Formally Accepted
30 Aug 2023 Acceptance Letter - Redoy Ranjan, Editor PONE-D-23-16421R1 Clinical presentation, microbiology, and prognostic factors of prosthetic valve endocarditis. Lessons learned from a large prospective registry. Dear Dr. Ramos-Martínez: I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department. If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org. If we can help with anything else, please email us at plosone@plos.org. Thank you for submitting your work to PLOS ONE and supporting open access. Kind regards, PLOS ONE Editorial Office Staff on behalf of Dr. Redoy Ranjan Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0290998.r004

Open letter on the publication of peer review reports

PLOS recognizes the benefits of transparency in the peer review process. Therefore, we enable the publication of all of the content of peer review and author responses alongside final, published articles. Reviewers remain anonymous, unless they choose to reveal their names.

We encourage other journals to join us in this initiative. We hope that our action inspires the community, including researchers, research funders, and research institutions, to recognize the benefits of published peer review reports for all parts of the research system.

Learn more at ASAPbio .