PONE-D-24-10329Systemic vasoconstriction and mortality in patients with heart failure and reduced ejection fraction: A cohort of patients who underwent non-invasive hemodynamic monitoringPLOS ONE

Dear Dr. OCHIAI,

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.

ACADEMIC EDITOR: We have now received comments from two experts in the field who have carefully reviewed your work. While they acknowledge the significance of your study and appreciate the thoroughness of your research, both reviewers have raised several critical issues that need to be addressed before we can proceed with the publication process.

Based on their feedback, we are requesting that you undertake a major revision of your manuscript.

Please submit your revised manuscript by Jul 24 2024 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.

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We look forward to receiving your revised manuscript.

Kind regards,

Yashendra Sethi

Academic Editor

PLOS ONE

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“São Paulo Research Foundation (FAPESP),

grant # 2008/03460-4

https://fapesp.br/en”

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Additional Editor Comments: The methodlogy has concerns which puts conclusions made in question. Please address all these comments in detail and make required changes.

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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: Partly

Reviewer #2: Yes

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

Reviewer #1: Yes

Reviewer #2: N/A

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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: No

Reviewer #2: No

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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: 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: In this article, the authors analyzed the use of Medflow (non invasive hemodynamic monitoring) to evaluate the systemic vascular resistance and determine if it predicts mortality in patients with ADHF.

We have some doubts about methodology:

1- How the SVRi was calculated (there is no mention of de CVP in the formula used). In the article it is mentioned that the SVRi was calculated by dividing the mean arterial pressure by the cardiac index.

2- In the baseline there is no mention about the use of inotropic drugs and if the acquisition of RVRi was priorily the introduction of inotropic

3- We think it is more appropriated to show the results in the final table (table2) divided in the two groups priorly analyzed (RVP <1200 and >1200). In the article the final analyses it was divided by outcome

Reviewer #2: I had the pleasure of reviewing the manuscript titled "Systemic Vasoconstriction and Mortality in Patients with Heart Failure and Reduced Ejection Fraction: A Cohort of Patients Who Underwent Non-Invasive Hemodynamic Monitoring." The manuscript effectively discusses and evaluates the prognostic significance of non-invasively identified systemic vasoconstriction in patients with decompensated heart failure and reduced ejection fraction (HFrEF). It should be free of grammatical and typographical errors. For instance, on line 141, the word "according" is missing a "to" after it. I recommend that the manuscript be reviewed for similar mistakes.

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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: Abdelrahman Gad

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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.

Attachments

Attachment

Submitted filename: Reviewer Comments PLOS.pdf

PONE-D-24-10329R1Systemic vasoconstriction and mortality in patients with heart failure and reduced ejection fraction: A cohort of patients who underwent non-invasive hemodynamic monitoringPLOS ONE

Dear Dr. OCHIAI,

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 Oct 06 2024 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,

Yashendra Sethi

Academic Editor

PLOS ONE

[Note: HTML markup is below. Please do not edit.]

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

Reviewer #2: All comments have been addressed

Reviewer #3: (No Response)

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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

Reviewer #3: Partly

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

Reviewer #1: Yes

Reviewer #2: N/A

Reviewer #3: No

**********

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

Reviewer #3: Yes

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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

Reviewer #3: 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: In this article, the authors analyzed de use of Medflow (non invasive hemodynamic monitoring) to evaluate the systemic vascular resistance and determine if it predicts mortality in patients with ADHF. The authors responded adequately to the questions requested.

Reviewer #2: I recommend that the manuscript titled "Systemic Vasoconstriction and Mortality in Patients with Heart Failure and Reduced Ejection Fraction: A Cohort of Patients Who Underwent Non-Invasive Hemodynamic Monitoring" be accepted for publication in PLoS One. The authors have addressed previous comments comprehensively and have corrected all grammatical and typographical errors.

Reviewer #3: The authors have assessed the utility of a non-invasive hemodynamic method to measure peripheral arterial resistance and to establish its relationship with mortality. This is an interesting study that might draw the attention of readers. However I have some comments to improve the quality of the manuscript.

1. Please add reference, page 3, lines 51 and 52. Mortality reduction with ACEi and hydralazine/nitrates.

2. Did the authors exclude patients with acute coronary syndromes as the cause of HF decompensation? Were there any cases of acute myocardial infarction?

3. The authors should clarify the exact moment when the hemodynamic evaluation was done. As I understood, it was done at admission, after the patients received the initial treatment and became stable. Is that correct? All patients underwent the hemodynamic evaluation within 24 h of admission?

4. Statistics: It is not clear whether the authors did multivariate analysis. Was this multivariate logistic regression? Why did the authors use logistic regression? Since they constructed survival curves, I assume they have the date in which the events occurred. I believe it would be more appropriate to use as an endpoint the time to the event of mortality and use Cox proportional hazard models (univariate and multivariate analysis) to assess whether vasoconstriction was independently associated with mortality. This is a small sample but the number of events is elevated, allowing for multivariate analysis.

5. I understood that this is a retrospective study since patients were included back in 2009. If so, please add this information in methods, line 68.

6. In table 3, we see that patients who died had higher LVEF% (24.1 vs 19.1%). This was unexpected. Did the authors find an explanation for that? Perhaps it was by chance?

7. Please add p value in figure 2.

8. Please add in the limitations that this is a small sample.

9. Please comment in the discussion that in the ESCAPE trial, adjusting medications by hemodynamic profiles in patients with advanced HF did not reduce events as compared with clinical assessment alone. In addition, hemodynamics have been outperformed by neuro-hormonal assessment. So it is important to show in the manuscript that vasoconstriction was a predictor of mortality regardless of BNP.

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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

Reviewer #2: Yes: Abdelrahman Gad

Reviewer #3: No

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[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.

Systemic vasoconstriction and mortality in patients with heart failure and reduced ejection fraction: A cohort of patients who underwent non-invasive hemodynamic monitoring

PONE-D-24-10329R2

Dear Dr. OCHIAI,

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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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,

Yashendra Sethi

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

Reviewer #3: 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: (No Response)

Reviewer #3: Yes

**********

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

Reviewer #1: (No Response)

Reviewer #3: 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: (No Response)

Reviewer #3: 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)

Reviewer #3: 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: (No Response)

Reviewer #3: The authors have addressed all issues. The manuscript is now clear and the limitations have been pointed out. No further comments.

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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

Reviewer #3: No

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