PONE-D-19-35111

The modified MIDA-Score predicts mid-term outcomes after interventional therapy of functional mitral regurgitation

PLOS ONE

Dear Dr. Öztürk,

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 by the expert reviewers during the review process and quoted below.

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Academic Editor

PLOS ONE

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Reviewers' comments:

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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: No

Reviewer #2: Yes

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2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: No

Reviewer #2: Yes

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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

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Reviewer #1: No

Reviewer #2: Yes

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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: Öztürk et al investigate the performance of various scoring systems in regard to the outcome of interventional treatment fo funktional miral regurgitation. The manuscript contains interesting informations and gives a precise summary of their investigation. However several major concerns remain:

- Check for spelling and grammar (eg line 36 „as“ instead of was, line 91 „life quality“ instead of quality of life, …), professional manuscript editing services is strongly recommended.

- There is not sufficient data in the manuscript to write „enables proper patient selection, adequate therapy decision, and timimg“ in the conclusion.

- Why was the inclusion set from 01/2014 until 08/2016? FU of 18 months would have allowed also patients from 2017 and 2018. As limited numbers are a major drwaback, the authors should consider to enlarge their cohort.

- „primary endpoint“ is a term which should be reserved for prospective trials. At least as soon as one speaks of primary endpoints also secondary endpoints should be defined.

- Description of echo assessment in detail does not offer any important informations as we all have to follow the guidelines and standard best practice.

- Generally spoken it seems a bit arbitrary that a combination of mortality and hospitalisation as endpoint was chosen. Probably the low mortality rate required an additional factor to reach at least a little statistical power. This is legitimate if explained in a clear and structured way. However The authors should think about a larger time frame or about a cooperation with other centers to significantly increase patient numbers.

Reviewer #2: In the present study, the authors tested the prognostic value of a previously proposed risk score for prognosis of patients with degenerative mitral regurgitation (DMR; MIDA Score, Grigioni-F et al, EHJ 2018) in a small, single-center cohort of patients with functional mitral regurgitation (FMR).

The original MIDA score parameter cut-off values were modified according to the results of published studies and meta-analyses in patients with FMR. With this information, a modified MIDAS-Score with new, adapted cut-off values was calculated and tested in the available small, single-center patient cohort with FMR and interventional treatment (Mitra-Clip or Cardioband). The modified MIDAS score performed well in this retrospectively analysed cohort, while the original MIDAS score (evaluated for a different disease entity) did not predict outcome. It is explained that the patient population with FMR differs from the DMR population and that the main differences in age and systolic function (LV EF) explain the need for a modified score (lines 240-248)

The present study is too small and not adequately designed to verify the prognostic value of the new, proposed modified MIDAS Score, as this is a retrospective analysis with all inherent limitations and with no group for comparison. However, it may stimulate further research in this area. These limitations are acknowledged by the authors and addressed in the “Limitations” and “Conclusion” section, however, this part of the limitations section could be expanded a bit and this could be stated a bit more clearly in the conclusions.

Specific questions/comments:

Limitations section: please add that and state clearly that this the retrospective analysis has a high risk for selection bias.

Line 404, Conclusion section: what is meant with “…primitively…”? Please rephrase.

Line 244: “pressure is often finding in those…” please rephrase to “..pressure is a frequent finding in those….”

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Reviewer #1: No

Reviewer #2: No

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PONE-D-19-35111R1

The modified MIDA-Score predicts mid-term outcomes after interventional therapy of functional mitral regurgitation

PLOS ONE

Dear Dr. Öztürk,

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 and quoted below.

We would appreciate receiving your revised manuscript by Jun 27 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,

Marc W. Merx, MD

Academic Editor

PLOS ONE

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: (No Response)

Reviewer #2: All comments have been addressed

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2. 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

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

**********

4. 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

**********

5. 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: Yes

**********

6. 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 authors,

the manuscript has improved and offers valuable insights into risk stratification of patients with functional MR. However a few concerns remain:

- the limited number of patients, which is already adressed in the "Limitations"

- Where do the auhors expect the most benefit? Pre-procedural by helping to decide which patient to treat and when to "defer"? Or post-procedural by guiding the intensity of follow-up care? Could the discussion and the conclusion precisely show the potential impact of the new score?

- native speaker revision or professional editing could improve spelling and Grammar still

Reviewer #2: I have reviewed the previous version, all my comments have been addressed appropriately, I have no additional comments and congratulate the authors for the manuscript

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Reviewer #1: No

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 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.

The modified MIDA-Score predicts mid-term outcomes after interventional therapy of functional mitral regurgitation

PONE-D-19-35111R2

Dear Dr. Öztürk,

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.

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Kind regards,

Marc W. Merx, MD

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: All comments have been addressed

**********

2. 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

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

**********

4. 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

**********

5. 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 Response)

**********

6. 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 Authors

congratulation for this sound manuscript which is almost ready for publication. Please check again for spelling and grammar, eg

- FMR is often finding in patients with chronic heart failure (CHF) and correlates with adverse prognosis, reduced quality of life, and high mortality [1].

Probalby you meant: FMR is an often finding…

- please write cardiac computed tomography instead of cardiac tomography

- Several studies presented superior outcomes, whereas there are many studies, which show any beneficial impact of the interventional FMR treatment compared to GDOMT alone [3], [12], [13], [16]. [17]. - What do you mean exactly?

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7. 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