PONE-D-20-12474

Rapid declines in systolic blood pressure are associated with an increase in pulse transit time

PLOS ONE

Dear Dr. Skjaervold,

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 address all comments pointed out by the reviewers with special attention to the difference between PTT derived from ECG R - PPG peak and ECG R - BP peak (SBP).
• In addition, the authors should clearly mention the weakness point of former works (identification of the gaps) and describe the novelties of the current investigation to justify us the paper deserves to be published in PLOS ONE.

Please submit your revised manuscript by Jul 16 2020 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,

Kenta Matsumura

Academic Editor

PLOS ONE

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2.  Thank you for stating the following in the Competing Interests section:

"NKS is chief medical officer and shareholder in Moon Labs, a medical-technology company that is prototyping a wearable biosensor; the company is currently not working with continuous blood pressure monitoring. SGS declares that he has no competing interests.".

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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: No

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

Reviewer #1: Yes

Reviewer #2: No

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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: Yes

Reviewer #2: Yes

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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 paper, the authors examined the correlation between pulse transit time(PTT) and systolic blood pressure(SBP) from the waveform database of an intensive care unit to monitor the rapid declines in blood pressure. The results of this study can be expected to lead to non-invasive, real-time detection of rapid declines in blood pressure. The focus of the paper is well phrased, including the problems with the method. However, I would still like make the following suggestions to hopefully improve the quality of the paper:

1. (L 59-60) More properly, the vascular unloading technique was originally proposed by Marey, and later by Shirer and Penaz (Matsumura et al., 2017, IEEE Tran. Biomed. Eng., 64(5), 1131-1137). So, the author needs to revise the phrase “originally proposed by Penaz in 1973” with adding references.

E. J. Marey, “Pression et vitesse du sang,” in Pbysiolotique Experimentale. vol. 2, Paris, France: G. Masson, 1876. Pp.307.

H. W. Shirer, “Blood pressure measuring methods,” Ire Trans. Biomed. Electron., vol. BME-9, pp. 116–125, Apr. 1962.

J. Penaz, “Photoelectric measurement of blood pressure, volume and flow in the finger,” in Proc. Dig. 10th Int. Conf. Med. Biological Eng., 1973, p. 104.

2. (L 78-79) A reference for conflicting papers should be added.

3.(L 153-154) What was the reason for using 21 samples in the averaging of SBP, PTT, and ABP?

4. (L 199-201) If the sample rate is 125 Hz, the time resolution should be 8 ms. However, why does Fig. 5(d) show a time resolution of 4 ms?

5. (Supplementary analysis(3)) Did the authors include the values of SBP,PTT-RA,HR obtained by the missing/ambiguous peaks in the calculation of SBPAV,PTT_RAAV,HRAV? If it is not included, the analysis is the same as the main analysis, and I think that it is not a proof of robustness.

Reviewer #2: The authors have investigated the relationship between declined systolic blood pressure (SBP) with pulse transit time (PTT) that was calculated from the ECG and arterial BP signals obtained in MIMIC database. The results indicate that the decrease of SBP is moderately associated with increase of PTT. Unlike the PTT calculated from ECG and photoplethysmogram (PTT), the PTT obtained from arterial BP would expect a higher correlation with BP, since it contains the direct information of BP rather than as an indirect estimate of BP. Therefore, I am not surprised with the results reported in this study. In addition, there are quite a lot study in the past decades or so on the relationship of the BP and PTT. I would therefore suggest the authors to clarify the significance of the study. My other concerns are:

1) PTT calculated from the peaks of arterial BP suffers from the reflective waveform which may impact the accuracy of the PTT;

2) I understand the synchronization issue between ECG and PPT, what about the similar issue in ECG and arterial BP?

3) For the moving average of PTT-RA, what is the time interval for the average?

4) In Fig. 6, there seems not too many data point for the estimate, but it was mentioned data from 511 subjects were included for the study

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Reviewer #1: No

Reviewer #2: Yes: Xiaorong Ding

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PONE-D-20-12474R1

Rapid declines in systolic blood pressure are associated with an increase in pulse transit time

PLOS ONE

Dear Dr. Skjaervold,

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:

• Please update Figure 5.

==============================

Please submit your revised manuscript by Oct 24 2020 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: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols

We look forward to receiving your revised manuscript.

Kind regards,

Kenta Matsumura

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: Partly

Reviewer #2: (No Response)

**********

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

Reviewer #1: Yes

Reviewer #2: (No Response)

**********

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: (No Response)

**********

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: (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: The manuscript has been revised well. I think this manuscript will be acceptable after some corrections have been done.

1) According to your answer, the correct time resolution for PTT-RA is 8 ms, but the correction is not reflected in Figure 5(b), (d) and (e) of the revised manuscript.

Reviewer #2: (No Response)

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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

[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.

Rapid declines in systolic blood pressure are associated with an increase in pulse transit time

PONE-D-20-12474R2

Dear Dr. Skjaervold,

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,

Kenta Matsumura

Academic Editor

PLOS ONE

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