PONE-D-21-25699The effectiveness of scoring balloon angioplasty in the treatment of chronic thromboembolic pulmonary hypertensionPLOS ONE

Dear Dr. Nakanishi,

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.

Both of the reviewers regard this experiment important, so please revise the manuscript.

Please submit your revised manuscript by Jan 24 2022 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,

Yoshiaki Taniyama, MD, PhD

Academic Editor

PLOS ONE

Journal Requirements:

When submitting your revision, we need you to address these additional requirements.

1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at

https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf

2. In your ethics statement in the manuscript and in the online submission form, please ensure that you have discussed whether all data/samples were fully anonymized before you accessed them and/or whether the IRB or ethics committee waived the requirement for informed consent. If patients provided informed written consent to have data/samples from their medical records used in research, please include this information.

3.  In your Data Availability statement, you have not specified where the minimal data set underlying the results described in your manuscript can be found. PLOS defines a study's minimal data set as the underlying data used to reach the conclusions drawn in the manuscript and any additional data required to replicate the reported study findings in their entirety. All PLOS journals require that the minimal data set be made fully available. For more information about our data policy, please see http://journals.plos.org/plosone/s/data-availability.

"Upon re-submitting your revised manuscript, please upload your study’s minimal underlying data set as either Supporting Information files or to a stable, public repository and include the relevant URLs, DOIs, or accession numbers within your revised cover letter. For a list of acceptable repositories, please see http://journals.plos.org/plosone/s/data-availability#loc-recommended-repositories. Any potentially identifying patient information must be fully anonymized.

Important: If there are ethical or legal restrictions to sharing your data publicly, please explain these restrictions in detail. Please see our guidelines for more information on what we consider unacceptable restrictions to publicly sharing data: http://journals.plos.org/plosone/s/data-availability#loc-unacceptable-data-access-restrictions. Note that it is not acceptable for the authors to be the sole named individuals responsible for ensuring data access.

We will update your Data Availability statement to reflect the information you provide in your cover letter.

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

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: Yes

Reviewer #2: No

**********

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

Reviewer #1: Yes

Reviewer #2: No

**********

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: No

**********

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

**********

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: Plain old balloon angioplasty (POBA) group vs the non-slip element (NSE) manuscript review.

Thank you so very much for the opportunity to review this interesting manuscript.

I am in agreement that we need to explore options for best delivery of balloon angioplasty to our chronic thromboembolic pulmonary hypertension patients.

I found this very interesting and helpful.

I do agree that additional study on a larger scale would be very helpful.

Your description of methods and statistics for sound and I do not recommend any significant change.

Comments regarding cost and implications regarding that may be helpful to the reader. That may be something to consider to add regarding catheter choice.

I agree with your comments and findings regarding effective blood flow improvement in the case of large balloon two-vessel ratio is something that needs to be explored further in the future as catheter selection may be based on pre-BPA assessment and does require further study to determine if this would improve outcomes.

I do recommend to review your conclusions as I think expanding this could be helpful to the reader.

Conclusion

2 NSE PTA scoring balloon did not show a significant improvement in pressure

3 gradient compared to conventional balloon. Nevertheless, NSE PTA scoring

4 balloon showed effective blood-flow improvement in the case of large balloon-to-

5 vessel ratio. NSE PTA scoring balloon was safe to use in BPA procedure. Our

6 results suggest that the use of the NSE PTA scoring balloon should be considered

7 as one of the treatment options for BPA.

Additional comments....................

When reading I did find a few typos noted below:

Page 10

6 pressure microcatheter on the guidewire was advanced to the tip of guiding

7 catheter where the 2 pressures, a tip of guiding catheter and pressure

8 microcatheter, were equalized after saline flash.

**FLUSH

Page 10

Δ Pressure ratio was defined as the difference between the pressure

13 ratio before and after BPA. Finally, the ratio of pressure ratios was defined as the

14 ratio between the before BPA pressure ratio and the after BPA pressure ration.

**RATIO

Question:

Page 13

11 was better controlled; mean right atrium pressure (RAP) was 8.0 ± 4.0 mmHg,

12 and pulmonary artery wedge pressure (PAWP) was 9.4 ± 3.5 mmHg.

**THIS NOTES BETTER CONTROLLED but likely should just be controlled as not comparing

Page 21

11 95% CI: -0.76 to -0.43, p < 0.01, respectively). Therefore, the NSE PTA scoring

12 balloon shows superior improvement in blood-flow after BPA over the

13 conventional balloon when the B/V ration is greater than 1.0.

**RATIO

Page 24

1 In addition, Soga et al. reported the usefulness of NSE PTA in experimental model

2 was enormously observed in the group with B/V ratio more than 1.0 [22].

**Would replace ENORMOUSLY here.

Page 25

Since the cross section of this element is wedge-shaped, high stress is

13 efficiently concentrated to the vessel wall. This may prevent severe dissociation

14 that reaches the media.

**DISSECTION

Page 26

1 There were several limitations in this study. First, this study was

2 conducted retrospectively at a single center with a limited sample size, not

3 randomized trial.

**A RANDOMONIZED TRIAL

Page 26

. In addition, we evaluated

11 only immediately after BPA. It has been reported that treated pulmonary arteries

12 are took time to dilate sufficiently.

**MAY TAKE TIME

Page 26

We need to investigate follow-up data to

13 conclude the effectiveness of scoring balloon in BPA procedure.

**PROCEDURES

Reviewer #2: PONE-D-21-25699: statistical review

SUMMARY. This is a retrospective study that compares the effect of the non-slip element percutaneous transluminal angioplasty (NSE PTA) on blood pressure ratios to the effect of plain-balloon treatments (POBA). The statistical analysis relies on t-test methods for comparing the NSE PTA and the POBA groups and on regression analysis for evaluating the effect of the use of NSE PTA scoring balloon on the pressure ratio in a subset of data where the balloon-to-vessel ratio exceeded 1.0. I have several major concerns about the statistical methods that have been employed in this paper.

MAJOR ISSUES

1. The statistical analysis focuses on the improvements of pressure ratios observed after Balloon pulmonary angioplasty (BPA) in 108 lesions, which are treated as independent observations. However, if I understood correctly, these lesions are clustered within 14 subjects and, as such, they may not be assumed as independent cases. Instead, they should be treated as repeated measures within a sample of 14 subjects. Repeated measures methods are available in SAS, which is the software used by the authors. Notice that the repeated measures structure of the data must be accounted for in both the ANOVA analysis that compares the NSE PTA and the POBA groups and in the regression analysis that focuses on the effect of the NSE PTA treatment.

2. This is a retrospective study and, as a result, subjects have not been randomly associated to the NSE PTA and the POBA groups. The authors should therefore provide evidence that these two groups do not significantly differ with respect to the biometrical variables that are summarized in Table 1. Otherwise, results could be biased by group-specific differences

3. The statistical analysis relies on the assumption that the dependent variables are normally distributed. The authors should provide some evidence that such assumption is realistic, otherwise all the p-values of the paper could be biased.

**********

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: 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.

The effectiveness of scoring balloon angioplasty in the treatment of chronic thromboembolic pulmonary hypertension

PONE-D-21-25699R1

Dear Dr. Nakanishi,

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.

An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org.

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,

Yoshiaki Taniyama, MD, PhD

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

The author responded the problems.

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 #2: 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 #2: (No Response)

**********

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

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 #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 #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 #2: (No Response)

**********

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 #2: No