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PONE-D-21-03871

Patient, hospital and country-level risk factors of all-cause mortality among patients with chronic heart failure: Prospective international cohort study

PLOS ONE

Dear Dr. PONGIGLIONE,

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We look forward to receiving your revised manuscript.

Kind regards,

Pasquale Abete

Academic Editor

PLOS ONE

Additional Editor Comments:

The manuscript is very interesting and topic. However I have only a concern about the importance of HF-related precipitating factors. Please see and discuss Testa G et al. Precipitating factors in younger and older adults with decompensated chronic heart failure: are they different? J Am Geriatr Soc. 2013 Oct;61(10):1827-8.

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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

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

Reviewer #1: Yes

Reviewer #2: Yes

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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: No

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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 the manuscript entitled Patient, hospital and country-level risk factors of all-cause mortality among patients with chronic heart failure: Prospective international cohort study, Pongiglione and co-authors report on patient-, hospital- and country-level characteristics associated with 1-year all-cause mortality among patients with chronic HF including geographic and hospital variation in mortality. On 9,277 patients with chronic HF in the prospective cohort study European Society of Cardiology Heart Failure Long Term, the Authors report an all-cause 1-year mortality rate, across 142 hospitals located in 22 countries, of 7.1% which varied between countries and hospitals. These mortality rates were directly associated with increasing age, diabetes, peripheral artery disease, higher NYHA class. Conversely, treatment with angiotensin-converting enzyme inhibitor and angiotensin receptor antagonists and being managed in an HF clinic were found protective against mortality. Interestingly, no other hospital-level characteristics, and no country-level healthcare characteristics were associated with 1-year mortality, suggesting that between-hospital variance might be crucial for HF patients’ outcomes.

Overall, this is a very interesting manuscript on a crucial topic in HF management. The aim is clear, data analysis is well conducted and reported, and results are well discussed. I consider the manuscript acceptable for publication as it stands.

Reviewer #2: The Authors explored hospital and country-level characteristics associated with 1-year all-cause mortality among patients with chronic HF and investigates geographic and hospital variation in mortality. They studied 9,277 patients with chronic HF enrolled between May 2011 and November 2017 in the prospective cohort study European Society of Cardiology Heart Failure Long Term registry across 142 hospitals, located in 22 countries. The mean age of the selected outpatients was 65 years and the all-cause 1- year mortality rate per 100 person-years was 7.1 and varied between countries (median 6.8, IQR 5.6-11.2) and hospitals (median 7.8, IQR 5.2-12.4). Mortality was associated with age (incidence rate ratio 1.03, 95% CI 1.02-1.04), diabetes mellitus (1.37, 1.15-1.63), peripheral artery disease (1.56, 1.27- 1.92), New York Heart Association class III/IV (1.91, 1.60-2.30), treatment with angiotensin-converting enzyme inhibitor and angiotensin receptor antagonists (0.71, 0.57-0.87) and HF clinic (0.64, 0.46-0.89). No other hospital-level characteristics, and no country-level healthcare characteristics were associated with 1-year mortality, with case-mix standardised variance between countries being very low and higher for hospitals (0.372).

I find the study of great interest, data support conclusion even if I suppose a possible role of a selection bias due to the selection made by European Society of Cardiology in the selection of hospital. The involved hospital are of recognize high quality and specifically devoted to cardiovascular disease. This reflect the great Job made the ESC in the diffusion of cardiovascular knowledge all over the Europe.

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Reviewer #1: No

Reviewer #2: Yes: Francesco CACCIATORE

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Patient, hospital and country-level risk factors of all-cause mortality among patients with chronic heart failure: Prospective international cohort study

PONE-D-21-03871R1

Dear Dr. PONGIGLIONE,

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,

Pasquale Abete

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

No further comments.

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: All comments have been addressed

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: Yes

Reviewer #2: Yes

**********

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

Reviewer #1: Yes

Reviewer #2: 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

Reviewer #2: 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

Reviewer #2: 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 #1: The Authors addressed all the comments form the reviewers. I confirm that the manuscript is acceptable for publication as it stands.

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