Pretransplant survival of patients with end-stage heart failure under competing risks

Kevin B. Smith; Tseeye Odugba Potters; Gabriel Lopez Zenarosa

doi:10.1371/journal.pone.0273100

Peer Review History

Original SubmissionAugust 20, 2021
7 Mar 2022 Decision Letter - Yoshihiro Fukumoto, Editor PONE-D-21-27074Pretransplant survival of patients with end-stage heart failure under competing risksPLOS ONE Dear Dr. Zenarosa, 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 Apr 21 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, Yoshihiro Fukumoto 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. Thank you for stating the following in the Acknowledgments Section of your manuscript: “This work was supported by funds provided by The University of North Carolina at Charlotte, University Professional Internship Program, Levine Scholars Program, and Honors College. Funding sources had no involvement in this study. The corresponding author affirms that he has listed everyone who contributed significantly to the work.” We note that you have provided funding information that is not currently declared in your Funding Statement. However, funding information should not appear in the Acknowledgments section or other areas of your manuscript. We will only publish funding information present in the Funding Statement section of the online submission form. Please remove any funding-related text from the manuscript and let us know how you would like to update your Funding Statement. Currently, your Funding Statement reads as follows: “This work was supported by funds provided by The University of North Carolina at Charlotte (GLZ, Faculty Research Grant, https://research.charlotte.edu/departments/center-research-excellence-cre/locating-funding/internal-funding-programs), University Professional Internship Program (KBS, https://career.charlotte.edu/upip), Levine Scholars Program (KBS, https://levinescholars.charlotte.edu), and Honors College (KBS, https://honorscollege.charlotte.edu). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.” Please include your amended statements within your cover letter; we will change the online submission form on your behalf. 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. 4. We note that you have indicated that data from this study are available upon request. PLOS only allows data to be available upon request if there are legal or ethical restrictions on sharing data publicly. For more information on unacceptable data access restrictions, please see http://journals.plos.org/plosone/s/data-availability#loc-unacceptable-data-access-restrictions. In your revised cover letter, please address the following prompts: a) If there are ethical or legal restrictions on sharing a de-identified data set, please explain them in detail (e.g., data contain potentially sensitive information, data are owned by a third-party organization, etc.) and who has imposed them (e.g., an ethics committee). Please also provide contact information for a data access committee, ethics committee, or other institutional body to which data requests may be sent. b) If there are no restrictions, please upload the minimal anonymized data set necessary to replicate your study findings as either Supporting Information files or to a stable, public repository and provide us with the relevant URLs, DOIs, or accession numbers. For a list of acceptable repositories, please see http://journals.plos.org/plosone/s/data-availability#loc-recommended-repositories. We will update your Data Availability statement on your behalf to reflect the information you provide. 5. Please include your full ethics statement in the ‘Methods’ section of your manuscript file. In your statement, please include the full name of the IRB or ethics committee who approved or waived your study, as well as whether or not you obtained informed written or verbal consent. If consent was waived for your study, please include this information in your statement as well. [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: Partly Reviewer #2: Partly ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: I Don't Know Reviewer #2: I Don't Know ****** 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: The authors reported the survival analyses of candidates for heart transplantation list under competing events of transplantation and MCSD implantation. The authors aimed to measure properly and estimate the survival probability of patients on the UNOS waitlist under competing risks to potentially highlight systematic biases and possible areas of improvement in organ allocation and patient status classification. However, this reviewer considers that this paper did not well meet the results for the objectives. This reviewer has several comments as described below. Major comments. 1. The study found high mortality and low attainment of transplantation in Status 2 patients. The authors should indicate the predictors of mortality in Status 2 patients. One of them might be small left ventricular diameters, such as restrictive cardiomyopathy, who cannot fit to VAD. 2. This reviewer feels that it was to overstate to conclude that all status2 patients have high mortality. The authors should explain what clinical features of status 2 had high mortality. 3. It is important to point out that the mortality rate of status 2 is higher than that of status 1 when the observation period is prolonged. It may indicate that the current organ distribution system is acceptable up to 300 days or 1002 days. The authors should add that point. 4. As the authors indicated, the results did not reflect the changes in status during the study period, which may lead to problems with the accuracy of the results. This was a big limitation. 5. Dissociation of the results between the cause-specific Hazards Model and the Subdistribution Hazards Model was difficult to understand, which should be explained more carefully. 6. In the Discussion section, the author described that Status2 patients had a higher rate of death than patients at higher priorities in Fig 2a. Was this Fig 3a? Reviewer #2: Describe heart-allocation policy and details about status /priority IA, 1B, 2 and 7. Figure 2 should present cumulative Incidence of Patient Survival event for each category of UNOS. Is the waiting list kept updated frequently as patient health conditions evolve? Did the priorities of patients analyzed in the study change accordingly? As shown in Fig 3a, during the first 500 days, the death probability in status 2 group is the lowest. Afterwards, the death probability rises up and exceeds d status 1B and 7 starting from day 1500. Label for each group should be distinguished. As shown in Fig.3 d, status 1b and status 2 has continuously received implantations through the entire 10 years, not as the authors stated “only Status 2 patients are receiving transplantation after 500 days and before 2000 days “. Provide waiting time information for transplantation and implantation in each group/status. The plot between waiting time for transplantation/ implantation and death should be provided, which are more valuable and informative. Page 8 lines 155-156 the authors wrote “ Fig 2a depicts that Status 2 patients have a higher rate of death 155 than patients at higher priorities.” However, Fig.2a did not provide any information about priorities. On page 9 Lin 185-186 Sentence “Long proposed is the idea that a score for patients with end-stage heart failure should be developed and utilized to judge priority..” What is a score? When is it collected? There are many grammar and typo errors. And English proof is needed. For example, on Page3 line 45 “ aged less than 16 years” ; On page 9 Lin 185-186 Sentence “Long proposed is the idea that a score for patients with end-stage heart failure should be developed and utilized to judge priority.. “ Full name for Abbreviation should be shown when it appears the first time. For example, UNOS. ****** 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. https://doi.org/10.1371/journal.pone.0273100.r001
Revision 1
25 May 2022 Author Response We are grateful to the publisher, academic editor, and two anonymous reviewers for their comments to improve our manuscript. Summarized in the following sections are the itemized comments accompanied by our corresponding responses and/or updates to the manuscript. Note: References to manuscript Line numbers are those of the change-tracked (marked-up) version. ------------------------------------------------------------ Academic Editor’s Comments and Authors’ Responses ------------------------------------------------------------ 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. Response: We use the PLOS ONE LaTeX template (https://journals.plos.org/plosone/s/latex), and: • We revised our manuscript to conform to the formatting guidelines, including correcting the author notes including affiliations, addresses, and corresponding authorship, as well as manually adjusting the default LaTeX template line-spacing for the title page. • We corrected the citations at the ends of sentences to appear before the punctuations. • We renamed the figure files as Fig1.tiff, Fig2.tiff, and Fig3.tiff. • We corrected the caption and legend of Table 3. • We adjusted for the LaTeX template automation to force Table 3 to appear within the manuscript rather than after the References. However, the LaTeX template still places Tables 1–3 on the pages following their first citations because they do not fit within the page under the paragraph in which they were first cited. 2. Thank you for stating the following in the Acknowledgments Section of your manuscript: “This work was supported by funds provided by The University of North Carolina at Charlotte, University Professional Internship Program, Levine Scholars Program, and Honors College. Funding sources had no involvement in this study. The corresponding author affirms that he has listed everyone who contributed significantly to the work.” We note that you have provided funding information that is not currently declared in your Funding Statement. However, funding information should not appear in the Acknowledgments section or other areas of your manuscript. We will only publish funding information present in the Funding Statement section of the online submission form. Please remove any funding-related text from the manuscript and let us know how you would like to update your Funding Statement. Currently, your Funding Statement reads as follows: “This work was supported by funds provided by The University of North Carolina at Charlotte (GLZ, Faculty Research Grant, https://research.charlotte.edu/departments/center-research-excellence-cre/locating-funding/internal-funding-programs), University Professional Internship Program (KBS, https://career.charlotte.edu/upip), Levine Scholars Program (KBS, https://levinescholars.charlotte.edu), and Honors College (KBS, https://honorscollege.charlotte.edu). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.” Please include your amended statements within your cover letter; we will change the online submission form on your behalf. Response: We removed the funding information from the Acknowledgements section and updated its contents as follows: The authors are grateful to the academic editor and two anonymous reviewers for their comments to earlier versions of this manuscript. The data reported here have been supplied by the United Network for Organ Sharing as the contractor for the Organ Procurement and Transplantation Network. The interpretation and reporting of these data are the responsibility of the author(s) and in no way should be seen as an official policy of or interpretation by the OPTN or the U.S. Government. We accept the funding statement as suggested, which is repeated here: This work was supported by funds provided by The University of North Carolina at Charlotte (GLZ, Faculty Research Grant, https://research.charlotte.edu/departments/center-research-excellence-cre/locating-funding/internal-funding-programs), University Professional Internship Program (KBS, https://career.charlotte.edu/upip), Levine Scholars Program (KBS, https://levinescholars.charlotte.edu), and Honors College (KBS, https://honorscollege.charlotte.edu). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. 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. Response: The UNOS Data Use Agreement signed by the UNC Charlotte liaison prohibits us from releasing the dataset without approval, which is quoted here: “You will neither release nor permit other to release the Data to any person (including media and subcontractors) except with the written approval of UNOS.” As a result, we would like to update our Data Availability Statement (as similarly stated in another PLOS ONE article using the same transplantation dataset, https://dx.doi.org/10.1371%2Fjournal.pone.0247789): Data cannot be shared publicly as it is owned by the United Network for Organ Sharing. We do not have permission to distribute the data, however, the data may be requested from the Organ Procurement and Transplantation Network. To obtain the data, a Data Use Agreement must be signed and approved by OPTN. Please refer the following URL: https://optn.transplant.hrsa.gov/data/request-data/. 4. We note that you have indicated that data from this study are available upon request. PLOS only allows data to be available upon request if there are legal or ethical restrictions on sharing data publicly. For more information on unacceptable data access restrictions, please see http://journals.plos.org/plosone/s/data-availability#loc-unacceptable-data-access-restrictions. In your revised cover letter, please address the following prompts: a) If there are ethical or legal restrictions on sharing a de-identified data set, please explain them in detail (e.g., data contain potentially sensitive information, data are owned by a third-party organization, etc.) and who has imposed them (e.g., an ethics committee). Please also provide contact information for a data access committee, ethics committee, or other institutional body to which data requests may be sent. b) If there are no restrictions, please upload the minimal anonymized data set necessary to replicate your study findings as either Supporting Information files or to a stable, public repository and provide us with the relevant URLs, DOIs, or accession numbers. For a list of acceptable repositories, please see http://journals.plos.org/plosone/s/data-availability#loc-recommended-repositories. We will update your Data Availability statement on your behalf to reflect the information you provide. Response: Kindly see our response to the preceding comment, which also applies to this comment. 5. Please include your full ethics statement in the ‘Methods’ section of your manuscript file. In your statement, please include the full name of the IRB or ethics committee who approved or waived your study, as well as whether or not you obtained informed written or verbal consent. If consent was waived for your study, please include this information in your statement as well. Response: We moved our full ethics statement from the Patient Selection subsection to a new Ethics subsection (Lines 35–42) at the beginning of the Methods section. ------------------------------------------------------------ Reviewer #1’s Comments and Authors’ Responses ------------------------------------------------------------ The authors reported the survival analyses of candidates for heart transplantation list under competing events of transplantation and MCSD implantation. The authors aimed to measure properly and estimate the survival probability of patients on the UNOS waitlist under competing risks to potentially highlight systematic biases and possible areas of improvement in organ allocation and patient status classification. However, this reviewer considers that this paper did not well meet the results for the objectives. This reviewer has several comments as described below. Major comments. 1. The study found high mortality and low attainment of transplantation in Status 2 patients. The authors should indicate the predictors of mortality in Status 2 patients. One of them might be small left ventricular diameters, such as restrictive cardiomyopathy, who cannot fit to VAD. Response: We include all at-listing variables considered in our models in Table 3. We state in Lines 64–70 that we considered all at-listing variables available from the data set and perform a mixed-selection method to derive the covariates for our models. Clinical characteristics, such as “small left ventricular diameters,” were not available in the dataset. Nevertheless, patients that may have been diagnosed with restrictive myopathy before or at listing would be contained within our primary diagnosis categorical variable. 2. This reviewer feels that it was to overstate to conclude that all status2 patients have high mortality. The authors should explain what clinical features of status 2 had high mortality. Response: We corrected our previous overstatement on Lines 162–163: Fig 3a depicts that the rate of death of Status 2 patients eventually surpasses those of patients at higher priorities. The death hazard ratios for the variables we analyzed are tabulated in Table 3. 3. It is important to point out that the mortality rate of status 2 is higher than that of status 1 when the observation period is prolonged. It may indicate that the current organ distribution system is acceptable up to 300 days or 1002 days. The authors should add that point. Response: We respectfully disagree: An equitable prioritization and allocation policy must attempt to maintain mortality curves ordered in accordance with priority, especially under competing risks: Status 2 patients have less alternatives. Throughout the 10-year study period, Status 2 patients have lower incidence of transplants (as imposed by their low priority), and the analyses revealed they also have lower incidence of implants. 4. As the authors indicated, the results did not reflect the changes in status during the study period, which may lead to problems with the accuracy of the results. This was a big limitation. Response: We agree; however, the available data does not allow for time-varying analyses, which we clarified in the new sentence added on Lines 174–176: However, the UNOS STAR files do not maintain historical changes in the variables we used (Table 3), thus prohibiting time-varying analyses. Nonetheless, we believe we modeled the problem as appropriately as contemporary methodology allows. 5. Dissociation of the results between the cause-specific Hazards Model and the Subdistribution Hazards Model was difficult to understand, which should be explained more carefully. Response: We revised the Predictors of Survival subsection of the Results section to clarify this dissociation in Lines 104–109: We note that the cause-specific hazard ratio (csHR) represents the rate of the event of interest in those patients that are event-free; thus, csHR provides the estimated etiological effects of the variables. In contrast, the subdistribution hazard ratio (sdHR) provides the prognostic effects of the variables. We also clarified the respective effects (in the context of an example) in the paragraph containing Lines 123–126: … we present csHRs and sdHRs to provide decision-makers the complete estimated etiological and prognostic effects, respectively, of the variables in our multivariate analyses. Additionally, we separated the discussion of exercising care in the interpretation of the subdistribution Hazards Model into its own paragraph: clarify this dissociation on Lines 104–109: The interpretation of the sdHR requires some care, however. We can assume that if a variable increases the subdistribution hazard, it will also increase the incidence of the event of interest, but we cannot conclude that these two are in the same magnitude. Thus, using the value of a covariate's sdHR only approximately describes the effect of that variable on the incidence of the event of interest. 6. In the Discussion section, the author described that Status2 patients had a higher rate of death than patients at higher priorities in Fig 2a. Was this Fig 3a? Response: We corrected the figure reference to Fig 3a. ------------------------------------------------------------ Reviewer #2’s Comments and Authors’ Responses ------------------------------------------------------------ 1. Describe heart-allocation policy and details about status /priority IA, 1B, 2 and 7. Response: We describe study-relevant information on heart allocation, including the citation to the full policy, as well as UNOS Statuses in Lines 51–54. 2. Figure 2 should present cumulative Incidence of Patient Survival event for each category of UNOS. Response: Cumulative incidences of patient survival for all UNOS Statuses are presented in Fig 3a. 3. Is the waiting list kept updated frequently as patient health conditions evolve? Did the priorities of patients analyzed in the study change accordingly? As shown in Fig 3a, during the first 500 days, the death probability in status 2 group is the lowest. Afterwards, the death probability rises up and exceeds d status 1B and 7 starting from day 1500. Response: Kindly refer to our responses to Reviewer 1’s Comments 4 and 5 above, which apply here. 4. Label for each group should be distinguished. As shown in Fig.3 d, status 1b and status 2 has continuously received implantations through the entire 10 years, not as the authors stated “only Status 2 patients are receiving transplantation after 500 days and before 2000 days “. Response: We distinguish UNOS Status for all panels of Fig 3 using the legend found in the upper left corner. Fig 3d displays the cumulative incidence of the transplantation event, not the implantation event. Fig 3d shows that the Status 1A and Status 1B cumulative incidence of transplantation are constant (i.e., flat curves) after 500 and 2000 days, respectively; this indicates that no transplants have since been accumulated for those statuses. 5. Provide waiting time information for transplantation and implantation in each group/status. The plot between waiting time for transplantation/ implantation and death should be provided, which are more valuable and informative. Response: Cumulative incidence curves incorporate waiting time by design; the step increases in Figs 3a, 3d, and 3g depict on the y-axis the incremental proportion of patients who experienced the event of interest (i.e., after the last step increase), and their waiting time is equal to the Days to Event on the x-axis when the step increase occurred. 6. Page 8 lines 155-156 the authors wrote “ Fig 2a depicts that Status 2 patients have a higher rate of death 155 than patients at higher priorities.” However, Fig.2a did not provide any information about priorities. Response: We corrected the figure reference to Fig 3a. 7. On page 9 Lin 185-186 Sentence “Long proposed is the idea that a score for patients with end-stage heart failure should be developed and utilized to judge priority..” What is a score? When is it collected? Response: We clarified the sentence with the following replacement on Lines 199–202: In contrast to other organ allocation policies, however, a prioritization model incorporating clinical characteristics has yet to be developed for the heart allocation policy. While different models have been proposed, a consensus on a prevailing model has yet to be reached. 8. There are many grammar and typo errors. And English proof is needed. For example, on Page3 line 45 “ aged less than 16 years” ; On page 9 Lin 185-186 Sentence “Long proposed is the idea that a score for patients with end-stage heart failure should be developed and utilized to judge priority.. “ Response: We respectfully disagree: The two examples given are grammatically correct. We proofread the manuscript again as suggested. 9. Full name for Abbreviation should be shown when it appears the first time. For example, UNOS. Response: We corrected this on Lines 23–24 and Lines 29–30. https://doi.org/10.1371/journal.pone.0273100.r002
3 Aug 2022 Decision Letter - Yoshihiro Fukumoto, Editor Pretransplant survival of patients with end-stage heart failure under competing risks PONE-D-21-27074R1 Dear Dr. Zenarosa, 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, Yoshihiro Fukumoto 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 #1: 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 #1: Partly ****** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: I Don't Know ****** 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 ****** 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 ****** 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: This reviewer has no further comment. The authors indicated to reconsider the classification of priorities in heart transplantation. It is a future challenge to determine what clinical characteristics of Status 2 patients are predictors of higher priority for heart transplantation. This reviewer hopes that this manuscript will serve as a starting point. ****** 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 ******** https://doi.org/10.1371/journal.pone.0273100.r003
Formally Accepted
5 Aug 2022 Acceptance Letter - Yoshihiro Fukumoto, Editor PONE-D-21-27074R1 Pretransplant survival of patients with end-stage heart failure under competing risks Dear Dr. Zenarosa: I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department. If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. 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. If we can help with anything else, please email us at plosone@plos.org. Thank you for submitting your work to PLOS ONE and supporting open access. Kind regards, PLOS ONE Editorial Office Staff on behalf of Dr. Yoshihiro Fukumoto Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0273100.r004

Open letter on the publication of peer review reports

PLOS recognizes the benefits of transparency in the peer review process. Therefore, we enable the publication of all of the content of peer review and author responses alongside final, published articles. Reviewers remain anonymous, unless they choose to reveal their names.

We encourage other journals to join us in this initiative. We hope that our action inspires the community, including researchers, research funders, and research institutions, to recognize the benefits of published peer review reports for all parts of the research system.

Learn more at ASAPbio .