Weight loss during follow-up in patients with acute heart failure: From the KCHF registry

Yuta Seko; Takao Kato; Takeshi Morimoto; Hidenori Yaku; Yasutaka Inuzuka; Yodo Tamaki; Neiko Ozasa; Masayuki Shiba; Erika Yamamoto; Yusuke Yoshikawa; Takeshi Kitai; Yugo Yamashita; Moritake Iguchi; Kazuya Nagao; Yuichi Kawase; Takashi Morinaga; Mamoru Toyofuku; Yutaka Furukawa; Kenji Ando; Kazushige Kadota; Yukihito Sato; Koichiro Kuwahara; Takeshi Kimura

doi:10.1371/journal.pone.0287637

Peer Review History

Original SubmissionDecember 14, 2022
18 Apr 2023 Decision Letter - Yoshihiro Fukumoto, Editor PONE-D-22-33948Weight Loss During Follow-up in Patients with Acute Heart Failure: from the KCHF registryPLOS ONE Dear Dr. Kato, 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 Jun 02 2023 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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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 ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: Yes ****** 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: No Reviewer #2: Yes ****** 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: In this prospective observational study, the authors analyzed the correlates and prognostic implications of weight loss at 6-month follow-up in patients discharged after an episode of AHF. Interestingly, weight loss was associated with worse clinical phenotype and outcomes. The authors should be congratulated for the original idea and the design of the study. Some points should be addressed to improve the quality of the work: - How was the 5% cut-off selected? Please detail. - Beyond the pre-specified cut-off, was weight loss linearly related to worse outcome? A spline curve could express this graphically. - No difference was reported in NT-proBNP levels at follow-up visit, despite the well-known correlation with body composition (e.g., 10.1016/j.jchf.2021.05.014). Please discuss. - It has been reported that the interaction between body composition and outcomes in HF patients may depend on HF etiology (i.e., ischemic vs. non-ischemic, 10.1177/2047487320927610). Please discuss. - The lack of physical training is a well-known determinant of both weight loss and poor outcome in HF patients. Did any patient undergo cardiac rehabilitation or training programs after the index hospitalization? In any case this should be matter of discussion. Reviewer #2: The manuscript by Seko and colleagues entitled “Weight Loss During Follow-up in Patients with Acute Heart Failure: from the KCHF registry” is very interesting. The management of weight in patients with heart failure is a huge problem. In general, weight gain suggests worsening of heart failure, and physicians and patients often aim to maintain or reduce body weight. On the other hand, this paper is highly significant in that it shows that weight loss does not necessarily lead to a favorable prognosis, as pointed out in this paper. However, I have some comments. Major comments 1.In patients with heart failure, weight loss is not all bad, and there appears to be malignant weight loss as shown in this paper and benign weight loss in patients who need “intended” reduction of body weight. Therefore, I think, if possible, it would be better to add subgroup analyzes such as baseline body weight-specific analysis. 2.To prevent weight loss in patients with heart failure, nutrition management and maintenance of activity are important, as the authors also stated. If possible, a more detailed baseline assessment of nutritional status (such as geriatric nutritional risk index) should be added. Among them, if the clinical characteristics of the group that loses weight in a group with maintained nutritional status is clarified, the target of intervention will be clarified a little more. 3.Why is the KM curve for all-cause death at 30 days getting different? I think factors other than weight loss are important. Minor comment It may be problematic that about 17% of all patients were analyzed. ****** 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. 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Please note that Supporting Information files do not need this step. https://doi.org/10.1371/journal.pone.0287637.r001
Revision 1
20 May 2023 Author Response Response We thank the reviewers for careful assessment and positive comments. The manuscript has been rechecked and the necessary changes have been made in accordance with the editors’ and reviewers’ suggestions. Reviewer #1: In this prospective observational study, the authors analyzed the correlates and prognostic implications of weight loss at 6-month follow-up in patients discharged after an episode of AHF. Interestingly, weight loss was associated with worse clinical phenotype and outcomes. The authors should be congratulated for the original idea and the design of the study. Some points should be addressed to improve the quality of the work: - How was the 5% cut-off selected? Please detail. Response Thank you for your valuable comment. We have selected 5% cut-off because cachexia is primarily defined as a loss of body mass of more than 5% in 12 months and previous studies also have selected 5% cut-off. (Reference [4, 6]) We have included some references in method section. (Page 8, line 12) - Beyond the pre-specified cut-off, was weight loss linearly related to worse outcome? A spline curve could express this graphically. Response Thank you for your careful assessment and suggestions. A spline curve could express weight loss linearly related to worse outcome graphically, but it is difficult to be used in this study in terms of low patient numbers. We have performed additionally sensitivity analysis classified into three groups as follows: ≥10% decrease in body weight, -10%< body weight change ≤ -5% and no weight loss (reference, -5%< body weight change) (S2 Fig). Higher decrease in body weight was related to worse outcome. - No difference was reported in NT-proBNP levels at follow-up visit, despite the well-known correlation with body composition (e.g., 10.1016/j.jchf.2021.05.014). Please discuss. Response Thank you for your careful assessment. We have included above reference and discussion as follows: “In our study, no difference was reported in NT-proBNP levels at follow-up visit due to the small number of patients with data and large variability.”(Page 19, line 10-12) - It has been reported that the interaction between body composition and outcomes in HF patients may depend on HF etiology (i.e., ischemic vs. non-ischemic, 10.1177/2047487320927610). Please discuss. Response Thank you for your careful assessment. Gentile et al. reported that higher BMI were associated with better outcome in non-ischaemic heart failure, but not in ischaemic heart failure. (Eur J Prev Cardiol. 2021;28(9):948-55.) In our study, we focus on weight loss, but we have evaluated the interactions between the ischemic etiology and the effects of weight loss relative to no weight loss on all-cause death. The ratio of ischemic etiology was not significant difference between weight loss and no weight loss group (Table 1). In addition, there was not interaction between weight loss and outcomes may depend on HF etiology in subgroup analysis (S5 Fig). - The lack of physical training is a well-known determinant of both weight loss and poor outcome in HF patients. Did any patient undergo cardiac rehabilitation or training programs after the index hospitalization? In any case this should be matter of discussion. Response Thank you for your careful assessment. In this study, we have no data about undergoing cardiac rehabilitation or training programs after the index hospitalization. We have added the next sentence in limitation section. “The lack of physical training is a well-known determinant of both weight loss and poor outcome in HF patients, but we have no data about undergoing cardiac rehabilitation or training programs after the index hospitalization.” (Page 20, line 11-13) Reviewer #2: The manuscript by Seko and colleagues entitled “Weight Loss During Follow-up in Patients with Acute Heart Failure: from the KCHF registry” is very interesting. The management of weight in patients with heart failure is a huge problem. In general, weight gain suggests worsening of heart failure, and physicians and patients often aim to maintain or reduce body weight. On the other hand, this paper is highly significant in that it shows that weight loss does not necessarily lead to a favorable prognosis, as pointed out in this paper. However, I have some comments. Major comments 1.In patients with heart failure, weight loss is not all bad, and there appears to be malignant weight loss as shown in this paper and benign weight loss in patients who need “intended” reduction of body weight. Therefore, I think, if possible, it would be better to add subgroup analyzes such as baseline body weight-specific analysis. Response Thank you for your careful assessment and valuable comments. We have evaluated the interactions between the subgroup factors such as age, etiology of HF, LVEF, BMI, albumin, anemia, geriatric nutritional risk index (GNRI) and the effects of weight loss relative to no weight loss on all-cause death after 6-month visit. There was no significant interaction between the effect of weight loss relative to no weight loss on the primary outcome measure and the subgroup factors (S5 Fig). We have includes the next sentences as follows: “In addition, there was a trend that patients with low BMI, low albumin levels, or low GNRI at 6-month visit were lily to have more risk when compared to those without, although there was no significant interaction between the effect of weight loss relative to no weight loss on the primary outcome measure and the subgroup factors.” (Page 19, line 18-22) 2.To prevent weight loss in patients with heart failure, nutrition management and maintenance of activity are important, as the authors also stated. If possible, a more detailed baseline assessment of nutritional status (such as geriatric nutritional risk index) should be added. Among them, if the clinical characteristics of the group that loses weight in a group with maintained nutritional status is clarified, the target of intervention will be clarified a little more. Response Thank you for your careful assessment and valuable comments. We have added the data of geriatric nutritional risk index and its change in Table 1. GNRI was lower and the increase of GNRI was less in the weight loss group (Table 1). We have included the next sentences as follows: “The increase of GNRI was less in the BW loss group. These data suggest the importance of nutrition management and maintenance of activity during the follow-up for patients with AHF.” (Page 19, line 16-18) 3.Why is the KM curve for all-cause death at 30 days getting different? I think factors other than weight loss are important. Response Thank you for your careful assessment and valuable comments. It is not clear why the KM curves for all-cause mortality at 30 days differ. There are two suggested reasons for this: 1) the number of patients enrolled in this study is relatively small and the KM curves for the two cohorts are not smoothed; 2) it is possible that some of the patients who lost weight after discharge may have further improved congestion, making it difficult for them to have events immediately after the starting point of 6 months after discharge. We have added into the Discussion sections (Page 18, line 11-15) Minor comment It may be problematic that about 17% of all patients were analyzed. Response Thank you for your careful assessment. We agree with your opinion and described it in the Limitation. Attachments Attachment Submitted filename: Response BW R1 seko 0514.docx https://doi.org/10.1371/journal.pone.0287637.r002
12 Jun 2023 Decision Letter - Yoshihiro Fukumoto, Editor Weight Loss During Follow-up in Patients with Acute Heart Failure: from the KCHF registry PONE-D-22-33948R1 Dear Dr. Kato, 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: (No Response) 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 #1: (No Response) Reviewer #2: Yes ****** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: (No Response) 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: (No Response) Reviewer #2: 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: (No Response) 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 authrors have signficantly improved the overall quality of their manuscript. I have no further comment. Reviewer #2: The previously mentioned issues have been adequately revised. I think it will have a impact on clinical practice. ****** 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 ******** https://doi.org/10.1371/journal.pone.0287637.r003
Formally Accepted
15 Jun 2023 Acceptance Letter - Yoshihiro Fukumoto, Editor PONE-D-22-33948R1 Weight Loss During Follow-up in Patients with Acute Heart Failure: from the KCHF registry Dear Dr. Kato: 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.0287637.r004

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