PONE-D-22-25832Association of epicardial fat with cardiac structure and function and cardiovascular outcomes: a protocol for systematic review and meta-analysisPLOS ONE

Dear Dr. Fukuta,

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Does the manuscript provide a valid rationale for the proposed study, with clearly identified and justified research questions?

The research question outlined is expected to address a valid academic problem or topic and contribute to the base of knowledge in the field.

Reviewer #1: Yes

Reviewer #2: Yes

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2. Is the protocol technically sound and planned in a manner that will lead to a meaningful outcome and allow testing the stated hypotheses?

The manuscript should describe the methods in sufficient detail to prevent undisclosed flexibility in the experimental procedure or analysis pipeline, including sufficient outcome-neutral conditions (e.g. necessary controls, absence of floor or ceiling effects) to test the proposed hypotheses and a statistical power analysis where applicable. As there may be aspects of the methodology and analysis which can only be refined once the work is undertaken, authors should outline potential assumptions and explicitly describe what aspects of the proposed analyses, if any, are exploratory.

Reviewer #1: Yes

Reviewer #2: No

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3. Is the methodology feasible and described in sufficient detail to allow the work to be replicable?

Descriptions of methods and materials in the protocol should be reported in sufficient detail for another researcher to reproduce all experiments and analyses. The protocol should describe the appropriate controls, sample size calculations, and replication needed to ensure that the data are robust and reproducible.

Reviewer #1: Yes

Reviewer #2: No

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4. Have the authors described where all data underlying the findings will be made available when the study is complete?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception, at the time of publication. 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: No

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Reviewer #1: Yes

Reviewer #2: Yes

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6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above and, if applicable, provide comments about issues authors must address before this protocol can be accepted for publication. You may also include additional comments for the author, including concerns about research or publication ethics.

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(Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: The authors provide an interesting and potential important manuscript describing "Association of epicardial fat with cardiac structure and function and cardiovascular

outcomes: a protocol for systematic review and meta-analysis", The main issues concerning this paper are those concerning the potential associations between epicardial fat and cardiac structure and function and cardiovascular outcomes

There are some weak points that need to be addressed by the authors.

Minor

1.In general, excess adipocytes have some negative effects on cardiovascular disease, but adipocytes, as an endocrine cell, can also secrete molecules such as adiponectin, omentin, and others that are beneficial for cardiovascular conditions. Adipose secreted factors in the context of non obesity, may play a protective role against cardiovascular. Patients older than 18 years were selected in the text for the determination of epicardial fat volume using MRI or CT and were not qualitative about whether the selected subjects were obese or not. So it is recommended to add grouping in this respect.

2.On the other hand, the age factor has a direct effect on mortality and prognosis, in order to better represent the effect of epicardial fat on CVD, the age grouping can be further increased under the premise that the data collected in the articles are comprehensive.

Reviewer #2: To my knowledge, there is no systematic literature review and meta-analysis that evaluates the association between epicardial fat and cardiac remodeling/cardiovascular events.

However, several criticisms should to be addressed:

- In the abstract, it is not clear the main aim of the study. In the secondary outcome, it is incorrect to consider the cardiac structure and dysfunction within the cardiovascular events. Furthermore, major outcomes, such as cardiovascular death and hospitalizations for HF, are already considered in the primary outcome of the study. Cardiac structure and function seems to be the main focus of the work, reading the title, but the primary objective concerns instead cardiovascular events. Clarify this aspect better.

- More details are required in the method section. Who and how many researchers will the literature search be performed? What is the combination of keywords used in the literature search? Will a hand search of references be performed upon completion? How often will the literature search be repeated?

- The authors plan to include only studies with measured cardiac structure and function on echocardiography. Could it also be useful to include studies that have measured cardiac structure and function with other less common methods, in order to have a more complete view of the literature?

- Regarding cardiovascular outcome, it is not clear why the authors want to focus their work only on heart failure?

- More details regarding the data extraction would be required.

- In the discussion section, among the possible mechanisms linking visceral fat and cardiac dysfunction, the authors cannot overlook the role of cardiac natriuretic peptides (see PMID: 36430893).

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Reviewer #1: No

Reviewer #2: No

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Attachments

Attachment

Submitted filename: Response-PONE-D-22-25832_R1.doc

Association of epicardial fat with cardiac structure and function and cardiovascular outcomes: a protocol for systematic review and meta-analysis

PONE-D-22-25832R1

Dear Dr. Fukuta,

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,

Roberto Magalhães Saraiva, MD, PhD

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Does the manuscript provide a valid rationale for the proposed study, with clearly identified and justified research questions?

The research question outlined is expected to address a valid academic problem or topic and contribute to the base of knowledge in the field.

Reviewer #1: Yes

Reviewer #2: Yes

**********

2. Is the protocol technically sound and planned in a manner that will lead to a meaningful outcome and allow testing the stated hypotheses?

The manuscript should describe the methods in sufficient detail to prevent undisclosed flexibility in the experimental procedure or analysis pipeline, including sufficient outcome-neutral conditions (e.g. necessary controls, absence of floor or ceiling effects) to test the proposed hypotheses and a statistical power analysis where applicable. As there may be aspects of the methodology and analysis which can only be refined once the work is undertaken, authors should outline potential assumptions and explicitly describe what aspects of the proposed analyses, if any, are exploratory.

Reviewer #1: Yes

Reviewer #2: Yes

**********

3. Is the methodology feasible and described in sufficient detail to allow the work to be replicable?

Descriptions of methods and materials in the protocol should be reported in sufficient detail for another researcher to reproduce all experiments and analyses. The protocol should describe the appropriate controls, sample size calculations, and replication needed to ensure that the data are robust and reproducible.

Reviewer #1: Yes

Reviewer #2: Yes

**********

4. Have the authors described where all data underlying the findings will be made available when the study is complete?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception, at the time of publication. 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 and, if applicable, provide comments about issues authors must address before this protocol can be accepted for publication. You may also include additional comments for the author, including concerns about research or publication ethics.

You may also provide optional suggestions and comments to authors that they might find helpful in planning their study.

(Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: All the problems have been solved. The article provides the association of empirical fat with cardiac structure and function and cardiovascular outcomes, which is important for the new research

Reviewer #2: The authors satisfied my previous requests and now the manuscript is clearer. I have no further suggestions.

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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: No

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