PONE-D-22-12074Stroke volume and cardiac output during 6 minute-walk tests are strong predictors of maximal oxygen uptake in people with strokePLOS ONE

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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: Yes

Reviewer #2: Yes

Reviewer #3: Yes

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

Reviewer #1: Yes

Reviewer #2: I Don't Know

Reviewer #3: I Don't Know

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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

Reviewer #3: 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

Reviewer #3: 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: Dear Editors nad Authors

Thank you for the opportunity to review the paper "Stroke volume and cardiac output during 6 minute-walk tests are strong predictors of maximal oxygen uptake in people with stroke" that concerns interesting research area - how to simply and objectively assess exercise capacity in patients with stroke. The authors use measurements of cardiovascular hemodynamics while 6MWT to predict VO2 peak in CPET. The concept is good because CPET is quite a difficult and time comsuming procedure. The results of the study revealed that VO2 peak can be estimated from 6MWT+ICG with clinically acceptable accuracy. The paper is well written.

I have only minor comments to be considered:

1. Abstract verses 16-18 - please put units after numbers, not in brackets .ie. "6MWD was 294+/-13 m"

2. Please rephrase the second sentence of Introduction (verses 29-31) to be more general and simply, i.e. "Peak oxygen consumption (VO2 peak) measured after stroke is usually significantly lower than in sex-matched...."

3. Please provide info how the data was transferred from Physioflow device to the Physioflow software - was it real-time wireless transfer or did you used memory card with post-exam cable transfer to PC?

4. Please comment on possible low quality of ICG while CPET and 6MWT - were any problems with it. If yes - please comment in Limitations.

5. verse 106 - provide full name of 6MWT in subheading

6. Table 1 - "Duration of stroke" - better "Time from stroke"

7. Verse 237-240 - the difference between model 2 and 3 are very slight, do not write that model 2 was better, it was comparable (as you correctly write in discussion).

Reviewer #2: Overall, a thorough and well-executed work that is clear and well described.

However, I am missing a small important addition in the introduction in relation to why this study is relevant, which the authors argue for in the discussion.

I would also find it relevant to elaborate a bit more about how these findings is relevant and can contribute in the clinical practice of stroke rehabilitation.

If the authors will consider the following comments, I find the manuscript contributing to gaining knowledge in the field of rehabilitation stroke survivors.

Comments for the manuscript:

In the introduction (line 27-52) I lack to understand why it is important to ass ICG to 6MWT in stroke patients? Why is it not enough just to have the 6MWT as an expression for the submaximal VO2test?

How and why is this important in the clinic?

It is presented in the discussion line 306-307, but this should be presented in the introduction as well.

Methods:

Line 71-72: Did you use a score for the ambulation ability such as FAC?

Line 85-87 “National Institutes of Health Stroke Scale (NIHSS), 86 Modified Rivermead Mobility Index (MRMI), Berg Balance Scale (BBS), Barthel 87 index (BI)”

The tests should be short described according to score range indication no/severe dependence/impairment and a reference.

Line 88-90: “Participants were then requested to attend the hospital cardiopulmonary laboratory 89 twice (72 hours apart) to perform, in random order, a progressive cycle ergometer test 90 or two 6MWTs (at least 30 minutes apart)”.

I do not understand. Did the participants first do the one kind of test and then the day after the other kind of test? I am not sure by the description in this section.

Line 193-194” The VO2peak achieved during CPET correlated well with 6MWD, peak HR and peak 194 CO during CPET, as well as with HR and CO recorded at the end of the 6MWT”

You are stating something but not presenting the numbers. Please present the numbers and move the statement to the discussion section.

Line 221: Table 2 MWD is not clarified in the table note

Line 224: Table 3 Why is MWD represented as it is stated that the besto of the two tests is represented. What is it compared with? The same goes with COPeak (L/min).

Regression analyses for prediction of VO2peak line 233-245 I must say it I rather confusing but I am not the right person to verify if this method is the correct.

Discussion:

Results line 185: 59 participants (52 males)

Howcome som many males? Do you have any comment on that?

Line 188-191:

“Peak HR and CO 189 during CPET were significantly higher than that achieved at the end of the 6MWT, with 190 a mean difference in HR and CO being 26 (95% CI: 22.3 to 29.3) and 2.3 (95% CI: 1.8 191 to 2.8), respectively.”

That is some mean differences, why?

Your findings: SV and CO measured during the 6MWT in stroke patients further improved the VO2peak prediction power compared to using 6MWD as a lone predictor.

–By how much is the prediction improved in including impedance cardiography (ICG) during a 6MWT?? And is the difference clinical relevant?

I would find it relevant to elaborate a bit more about how these findings is relevant and can contribute in the clinical practice of stroke rehabilitation.

Reviewer #3: Dear Authors

I appreciate the authors and PLOS ONE for the opportunity to evaluate this paper. The authors led an interesting study that the prediction of VO2peak can be improved by the inclusion of cardiovascular indices derived by impedance cardiography (ICG) during the 6MWT in people with stroke. They found that the prediction equation with inclusion of cardio dynamic variables: 16.855 + (-0.060 x age) + (0.196 x BMI) +20 (0.01 x 6MWD) + (-0.416 x SV6MWT) + (3.587 x CO 6MWT) has a higher squared multiple correlation (R2) and a lower standard error of estimate (SEE) and SEE% compared to the equation using 6MWD as the only predictor. These findings will be of interest to clinicians, as well as researchers in the field.

I have following concerns.

Introduction

1. What is the clinical implication of this study? Is it significant that it has been conducted in young adults but not in stroke? If so, I would think a comparison with trends in young adults would be in order.

Methods

2. Are patients with arrhythmias excluded? There are descriptions of uncontrolled arrhythmias, but what about controlled Af? Additionally, were there any patients with brainstem lesions? There may be some impact because the respiratory and circulatory centers are located.

Results

3. A patient flow chart of inclusion/exclusion criteria may be helpful to understand the patient’s characteristics.

4. My greatest concern is that most of the subjects are male. It is mentioned in the limitation, but we need to be very careful about generalizing. Authors should consider presenting male-only results.

5. I think the p-value in Table 1 should be a specific number, not p>0.05.

6. Kidney disease and pulmonary disease were recorded, but there are no data in Table1.

7. Table 6 “At the end of end”. Is it “At the end of 6MWT”?

Discussion

8. It may not be appropriate to apply inferences drawn from our data analysis to female patients, however the pattern of response to exercise stress between male and female patients appeared to be similar.

The tendency of the pattern of response may be similar, but the degree to which they are different is quite different.

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Reviewer #1: Yes: Paweł Krzesiński

Reviewer #2: No

Reviewer #3: No

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Stroke volume and cardiac output during 6 minute-walk tests are strong predictors of maximal oxygen uptake in people after stroke

PONE-D-22-12074R1

Dear Dr. Jones,

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,

Shane Patman, PhD

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 #2: 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 #2: Yes

Reviewer #3: Yes

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

Reviewer #2: Yes

Reviewer #3: I Don't Know

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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: Yes

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 #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 #2: Thank you for including me in this process and for having the confidence in letting me review your interesting work. Comments and suggestions for improvement have been met and made and I recommend the article to be published.

Reviewer #3: Dear Authors

The authors did an excellent job addressing my previous comments and their response seems reasonable. The manuscript and associated figures are now more informative. I have no further comments.

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If you choose “no”, your identity will remain anonymous but your review may still be made public.

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Reviewer #2: Yes: Henriette Busk

Reviewer #3: No

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Submitted filename: Letter to the editor August 2022.docx