PONE-D-22-32676Contrasting the potential benefits of early invasive coronary angiography in acute and chronic myocardial injury patterns.PLOS ONE

Dear Dr. Eng-Frost,

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. You address an important clinical question particularly in the setting of troponin elevation perioperatively in non cardiac surgery.The majority of the troponin elevations are assumed to be due to type 2 MIs and are deemed not to require ICA.What the reader needs from your paper is clear indications when to require ICA in the absence of clear ECG changes. Should they rely on the extent of the troponin elevation or should they require any additional information such as wall motion abnormalities in individuals who had a baseline echo that did not reveal any. Or other clear indications on who might benefit and in whom it would be a waste of resources without any benefit to the patient.

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Reviewer #1: Yes

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

Reviewer #1: 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

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Reviewer #1: Yes

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5. Review Comments to the Author

Reviewer #1: The paper deals with a relevant problem raised by the introduction of hs-cTnC assay. A non negligible number of patients have values above 99th percentile of URL without evident signs of ischemia, with or without dynamic changes. This occurs in patients referred to Emergency Department but also in other settings for example after non cardiac surgery. In both conditions outcome is significantly worse in comparison without hs-cTnC elevation. The authors discuss the role of coronary angiography in different groups of patients . It is not clear indication to angiography in patients without clinical signs of ischemia as well in paragraph "Association between coronary angiography and 12-month death or recurrent ACS by hs-cTnT pattern" they report the sentence "This association was not observed inpatients with chronic myocardial injury who received early ICA, with similar rates of overall death or MI with a higher rate of recurrent myocardial infarction (ICA: 27, 3.6%;

vs no ICA:10; 10.6% p=0.0019) but a lower rate of all-cause mortality (ICA: 0, 0.0% vs no ICA: 80, 10.8%; p=0.0008)" that is not clear . A table or a figure comparing the groups may help the reader . The discussion is long and dispersive and may be shortened and simplified

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PONE-D-22-32676R1Contrasting the potential benefits of early invasive coronary angiography in acute and chronic myocardial injury patterns.PLOS ONE

Dear Dr. Joanne Eng-Frost,

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 end of April.  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,

Shukri AlSaif

Academic Editor

PLOS ONE

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Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

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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)

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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

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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

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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

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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: The paper is interesting and outlines the difficulties in the interpretation of high hs-TnT levels . In figure 1 I do not understand who is inserted in the third group (acute MI??). In table II angiography has been performed in 182 patients . Overall coronary revascularisation was reported in 83 (45.6%) but thereafter are described PCI 20 (11.0%) and CABG 102 (56.0%) ( a total of 122 patients) . The numbers are not concordant. T We agree that hs TnT is related to long term survival both in patients with chronic or changing troponin levels . Whether patients in RAPID study were included without ECG examination how was diagnosis of type of MI made ? The patients from the two study had ED evaluation for chest pain ? It should be reported in the description of the study. The number of patients with chronic myocardial injury underwent angiography was close to 15% of the whole population and only a small number were studied at 12 months with 3.7% of further revascularization Overall mortality was not different from the other group , the other end points are differently reported in table 2 and 3 ( for example ACS death in table 2 is not reported in table 3, Death, MI, and unstable angina in table 3 ) . A table comparing the two groups may be useful . The paper is long and discussion not easy to follow. Please simplify fo the reader.

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Reviewer #1: No

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Contrasting the potential benefits of early invasive coronary angiography in acute and chronic myocardial injury patterns.

PONE-D-22-32676R2

Dear Dr. Eng-Frost,

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.

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Kind regards,

Shukri AlSaif

Academic Editor

PLOS ONE