Differences in right-to-left vs left-to-right interventricular conduction times in patients indicated to cardiac resynchronization therapy

David Pospisil; Tomas Novotny; Jiri Jarkovsky; Barbora Farkasova; Milan Kozak; Lubomir Krivan; Jitka Vlasinova; Petr Kala; Milan Sepsi

doi:10.1371/journal.pone.0228731

Peer Review History

Original SubmissionNovember 24, 2019
20 Dec 2019 Decision Letter - Giuseppe Coppola, Editor PONE-D-19-32599 Differences in right-to-left vs left-to-right interventricular conduction times in patients indicated to cardiac resynchronization therapy PLOS ONE Dear Dr. Sepsi 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. We would appreciate receiving your revised manuscript by Feb 03 2020 11:59PM. When you are 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. If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. To enhance the reproducibility of your results, we recommend that if applicable you deposit your laboratory protocols in protocols.io, where a protocol can be assigned its own identifier (DOI) such that it can be cited independently in the future. For instructions see: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols 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). This letter should be uploaded as separate file and labeled 'Response to Reviewers'. A marked-up copy of your manuscript that highlights changes made to the original version. This file should be uploaded as separate file and labeled 'Revised Manuscript with Track Changes'. An unmarked version of your revised paper without tracked changes. This file should be uploaded as separate file and labeled 'Manuscript'. Please note while forming your response, if your article is accepted, you may have the opportunity to make the peer review history publicly available. The record will include editor decision letters (with reviews) and your responses to reviewer comments. If eligible, we will contact you to opt in or out. We look forward to receiving your revised manuscript. Kind regards, Giuseppe Coppola 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 http://www.plosone.org/attachments/PLOSOne_formatting_sample_main_body.pdf and http://www.plosone.org/attachments/PLOSOne_formatting_sample_title_authors_affiliations.pdf 2. We note that you have indicated that data from this study are available upon request. PLOS only allows data to be available upon request if there are legal or ethical restrictions on sharing data publicly. For information on unacceptable data access restrictions, please see http://journals.plos.org/plosone/s/data-availability#loc-unacceptable-data-access-restrictions. In your revised cover letter, please address the following prompts: a) If there are ethical or legal restrictions on sharing a de-identified data set, please explain them in detail (e.g., data contain potentially identifying or sensitive patient information) and who has imposed them (e.g., an ethics committee). Please also provide contact information for a data access committee, ethics committee, or other institutional body to which data requests may be sent. b) If there are no restrictions, please upload the minimal anonymized data set necessary to replicate your study findings as either Supporting Information files or to a stable, public repository and provide us with the relevant URLs, DOIs, or accession numbers. Please see http://www.bmj.com/content/340/bmj.c181.long for guidelines on how to de-identify and prepare clinical data for publication. For a list of acceptable repositories, please see http://journals.plos.org/plosone/s/data-availability#loc-recommended-repositories. We will update your Data Availability statement on your behalf to reflect the information you provide. Additional Editor Comments (if provided): Kind author, your manuscript underwent three different reviewers; your paper is quite interesting but it does present some methodological problems. We cannot accept as it is; you will find all the comments and criticisms underlined by reviewers. We hope you could answer point by point to resubmit a revised version of your manuscript. [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: Partly Reviewer #3: Yes ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: Yes Reviewer #3: 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 Reviewer #3: 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: Yes Reviewer #2: No Reviewer #3: 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 author, the paper is well written and the topic is very interesting. The protocol is clear and precise while results appear hard to understand after a single reading and should be improved considering that they seem to be a long list of figures and tables description. Moreover an important limitation of this study is the small number of enrolled patients. At least, have you any data about response to resynchronization according to difference between inter-ventricular delay? Regarding this topic I would like to suggest this paper regarding QRS index that can be considered a surrogate of reduced interventricular conduction delay: Magnitude of QRS duration reduction after biventricular pacing identifies responders to cardiac resynchronization therapy. Coppola G, Ciaramitaro G, Stabile G, DOnofrio A, Palmisano P, Carità P, Mascioli G, Pecora D, De Simone A, Marini M, Rapacciuolo A, Savarese G, Maglia G, Pepi P, Padeletti L, Pierantozzi A, Arena G, Giovannini T, Caico SI, Nugara C, Ajello L, Malacrida M, Corrado E. Int J Cardiol. 2016 Oct 15;221:450-5. Reviewer #2: The paper from Sepsi and coll. is quite interesting but it does present some methodological problems. 1. The position of the RV lead could have had an impact on results. It is not simply a matter of how many RV leads have been implanted in a group or in another, but that changing the RV lead position IN THAT patients could have lead to completely different results and this impacts negatively on the study itself 2. The definition itself of "septal RV lead" is quite generical: which part of the septum? Hissian, parahissiam, septal RVOT? Again, this could have changed everything 3. The conclusions on correction on RV-LV lead delay (or viceversa; page 17, lines 213 - 214) and results of CRT is too simplicistic. FREEDOM Trial on use of QuickOpt did not demonstrate any benefit from this approach (it is almost the same concept, because the algorhitm measure the RV-LV delay during RV pacing and LV-RV delay during LV pacing and adjusts the VV interval so that the activation front is simultaneous) Furthermore, I do not understand (Abstract, page 8, line 30) what does that < 5 ms mean: could the Authors make it clearer or at least explain in the revision letter the meaning of this statement. Finally, the whole manuscript needs a deep english language revision because some passages are unclear. Reviewer #3: Cardiac resynchronization therapy (CRT) is an established treatment for patients with heart failure (HF), impaired left ventricular (LV) function, and wide QRS complex. Pospisil et al. described the phenomenon of interventricular conduction time differences and assessed relationship to various clinical and electrophysiological parameters. In fact the differences in conduction times from right ventricle to left ventricle and from left ventricle to right ventricle respectively were observed during biventricular devices implantation when changing pacing vector direction. In this study a pronounced differences (often up to 35 ms) were observed in substantial part of patients with dilatative cardiomyopathy (DCM), while this phenomenon was much less common in patients with coronary artery disease (CAD). The study is very interesting, presented in an appropriate fashion and are supported by interesting data. A limitation is represented by the small sample number (62 patients) to draw conclusions although the idea from a pathophysiological point of view is acceptable. Moreover it would be interesting to point out that other studies have also previously evaluated importance of CRT (see: “Non-responders to cardiac resynchronization therapy: Insights from multimodality imaging and electrocardiography. A brief review”, Doi: 10.1016/j.ijcard.2016.09.037). This would certainly increase the the article's quality. In conclusion, given the overall work, I accept manuscript with minor revision concerning a small implementation of bibliography, reporting the aforementioned work and other. ****** 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: No Reviewer #2: Yes: Giosue Mascioli Reviewer #3: 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 to be viewed.] 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 us at figures@plos.org. Please note that Supporting Information files do not need this step. https://doi.org/10.1371/journal.pone.0228731.r001
Revision 1
16 Jan 2020 Author Response PLoS ONE Brno, January 8, 2020 Editorial Office Dear editor, Please find attached our revised manuscript called Differences in right-to-left vs. left-to-right interventricular conduction times in patients indicated for cardiac resynchronization therapy by David Pospisil et al., (PONE-D-19-32599). Thank you for your invitation to submit a revised version of the manuscript. We highly appreciate the opportunity to respond to reviewer’s suggestions on the paper to clarify all questions and to meet PLoS ONE’s publication criteria. We look forward to hearing from you regarding our submission. We would be glad to respond to any further questions and comments that you may have. Best regards On behalf of all the authors Milan Sepsi, MD, PhD Department of Internal Medicine and Cardiology University Hospital Brno, Masaryk University, Jihlavska 20, 625 00 Brno, Czech Republic Phone: +420 777 227 346, Fax: +420 53223 2611, E-mail: sepsi.milan@fnbrno.cz Response to Reviewer #1: Dear reviewer, thank you for your valuable time and useful contribution. We highly appreciate your inputs you given to improve the manuscript. We hope you will find our explanations and manuscript edits enough to your convenience. A point-by-point reactions to your comments and critics are written below directly into received texts using blue colored italic font. Attached file “Revised Manuscript with Track Changes” contains marked revisions made in the manuscript. Dear author, the paper is well written, and the topic is very interesting. The protocol is clear and precise while results appear hard to understand after a single reading and should be improved considering that they seem to be a long list of figures and tables description. According to your proposition some corrections of the text have been applied. Nevertheless, the text of the “Results” section is quite short, substantial part of information is present in figures and their captions (which are inserted in the text of the manuscript immediately following the paragraph in which the figure is first cited). Moreover, an important limitation of this study is the small number of enrolled patients. We agree that the number is small and we have commented it in the limitations. Nevertheless, as a pilot study it can be sufficient to draw conclusions from a pathophysiological point of view. It is clear it deserves a further study on larger set of patients. At least, have you any data about response to resynchronization according to difference between inter-ventricular delay? Unfortunately, not yet. We are preparing a study to evaluate the phenomenon according to QRS width and responsiveness to CRT rigorously. Regarding this topic I would like to suggest this paper regarding QRS index that can be considered a surrogate of reduced interventricular conduction delay: Magnitude of QRS duration reduction after biventricular pacing identifies responders to cardiac resynchronization therapy. Coppola G, Ciaramitaro G, Stabile G, DOnofrio A, Palmisano P, Carità P, Mascioli G, Pecora D, De Simone A, Marini M, Rapacciuolo A, Savarese G, Maglia G, Pepi P, Padeletti L, Pierantozzi A, Arena G, Giovannini T, Caico SI, Nugara C, Ajello L, Malacrida M, Corrado E. Int J Cardiol. 2016 Oct 15;221:450-5. We find suggested paper very interesting regarding our topic and it has been added to the manuscript. Response to Reviewer #2: Dear Dr. Mascioli, thank you for your valuable time and useful contribution. We highly appreciate your inputs you given to improve the manuscript. We hope you will find our explanations and manuscript edits enough to your convenience. A point-by-point reactions to your comments and critics are written below directly into received texts using blue colored italic font. Attached file “Revised Manuscript with Track Changes” contains marked revisions made in the manuscript. Reviewer #2: The paper from Sepsi and coll. is quite interesting, but it does present some methodological problems. 1. The position of the RV lead could have had an impact on results. It is not simply a matter of how many RV leads have been implanted in a group or in another, but that changing the RV lead position IN THAT patients could have lead to completely different results and this impacts negatively on the study itself. Of course, we considered that RV placement might have a significant impact to the interventricular conduction time and it obviously has. What we want to show is the fact that the differences of RV→LV and LV→RV conduction times are present regardless of RV lead placement in a given position. 2. The definition itself of "septal RV lead" is quite generical: which part of the septum? Hissian, parahissian, septal RVOT? Again, this could have changed everything. The information on septal vs apical position is based on implanting physician’s declaration. Unfortunately more detailed information on the lead position is not available. The aim of our manuscript is introduction of the phenomenon. Relationships to particular positions would require its study on larger group of patients. 3. The conclusions on correction on RV-LV lead delay (or viceversa; page 17, lines 213 - 214) and results of CRT is too simplicistic. FREEDOM Trial on use of QuickOpt did not demonstrate any benefit from this approach (it is almost the same concept, because the algorhitm measure the RV-LV delay during RV pacing and LV-RV delay during LV pacing and adjusts the VV interval so that the activation front is simultaneous) The text was modified. Furthermore, I do not understand (Abstract, page 8, line 30) what does that < 5 ms mean: could the Authors make it clearer or at least explain in the revision letter the meaning of this statement. In original text, there was a mistake – thank you: we considered interventricular conduction times difference lower than 5 milliseconds (ms) as a bidirectionally comparable conduction (because of measurement error), so. statement < 5 ms corrected to “>5 ms”. Finally, the whole manuscript needs a deep English language revision because some passages are unclear. A complete grammar, language and terminology check was done by scientific manuscript editing service to fit the US-English standards. We include PDF file with certification by Proof.Reading.Service.Com Ltd. Response to Reviewer #3: Dear reviewer, thank you for your valuable time and useful contribution. We highly appreciate your inputs you given to improve the manuscript. We hope you will find our explanations and manuscript edits enough to your convenience. A point-by-point reactions to your comments and critics are written below directly into received texts using blue colored font. Attached file “Revised Manuscript with Track Changes” contains marked revisions made in the manuscript. Reviewer #3: Cardiac resynchronization therapy (CRT) is an established treatment for patients with heart failure (HF), impaired left ventricular (LV) function, and wide QRS complex. Pospisil et al. described the phenomenon of interventricular conduction time differences and assessed relationship to various clinical and electrophysiological parameters. In fact the differences in conduction times from right ventricle to left ventricle and from left ventricle to right ventricle respectively were observed during biventricular devices implantation when changing pacing vector direction. In this study a pronounced differences (often up to 35 ms) were observed in substantial part of patients with dilatative cardiomyopathy (DCM), while this phenomenon was much less common in patients with coronary artery disease (CAD). The study is very interesting, presented in an appropriate fashion and are supported by interesting data. A limitation is represented by the small sample number (62 patients) to draw conclusions although the idea from a pathophysiological point of view is acceptable. Moreover, it would be interesting to point out that other studies have also previously evaluated importance of CRT (see: “Non-responders to cardiac resynchronization therapy: Insights from multimodality imaging and electrocardiography. A brief review”, Doi: 10.1016/j.ijcard.2016.09.037). This would certainly increase the article's quality. In conclusion, given the overall work, I accept manuscript with minor revision concerning a small implementation of bibliography, reporting the aforementioned work and other. We find the suggested paper very interesting regarding our topic and it has been added to the manuscript. Attachments Attachment Submitted filename: Response to Reviewers.docx https://doi.org/10.1371/journal.pone.0228731.r002
23 Jan 2020 Decision Letter - Giuseppe Coppola, Editor Differences in right-to-left vs left-to-right interventricular conduction times in patients indicated to cardiac resynchronization therapy PONE-D-19-32599R1 Dear Dr. Milan Sepsi, We are pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it complies with all outstanding technical requirements. Within one week, you will receive an e-mail containing information on the amendments required prior to publication. When all required modifications have been addressed, you will receive a formal acceptance letter and your manuscript will proceed to our production department and be scheduled for publication. Shortly after the formal acceptance letter is sent, an invoice for payment will follow. To ensure an efficient production and billing process, please log into Editorial Manager at https://www.editorialmanager.com/pone/, click the "Update My Information" link at the top of the page, and update your user information. 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 enable them to help maximize its impact. If they will be preparing press materials for this manuscript, you must inform our press team as soon as possible and 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. With kind regards, Giuseppe Coppola Academic Editor PLOS ONE Additional Editor Comments (optional): Manuscript underwent language revision. Authors have answerd to all reviewrs coments and criticisms when it was possible considering this manuscript a pilot study. Reviewers' comments: https://doi.org/10.1371/journal.pone.0228731.r003
Formally Accepted
28 Jan 2020 Acceptance Letter - Giuseppe Coppola, Editor PONE-D-19-32599R1 Differences in right-to-left vs left-to-right interventricular conduction times in patients indicated to cardiac resynchronization therapy Dear Dr. Sepsi: I am 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 notify them about your upcoming paper at this point, to enable them to help maximize its impact. If they will be preparing press materials for this manuscript, 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. For any other questions or concerns, please email plosone@plos.org. Thank you for submitting your work to PLOS ONE. With kind regards, PLOS ONE Editorial Office Staff on behalf of Dr. Giuseppe Coppola Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0228731.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 .