Etiology, characteristics and occurrence of heart diseases in rural Lesotho (ECHO-Lesotho): A retrospective echocardiography cohort study

Nzola John Ndongala; Callixtina Maepa; Emmanuel Nyondo; Alain Amstutz; Baptiste du Reau de la Gaignonnière

doi:10.1371/journal.pone.0278406

Peer Review History

Original SubmissionDecember 17, 2021
12 Jul 2022 Decision Letter - Lucio Careddu, Editor PONE-D-21-39404Etiology, characteristics and occurrence of heart diseases in rural Lesotho (ECHO-Lesotho): A retrospective echocardiography cohort studyPLOS ONE Dear Dr. Amstutz, 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 Aug 26 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. 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If you wish to make changes to your Data Availability statement, please describe these changes in your cover letter and we will update your Data Availability statement to reflect the information you provide. 4. Please include captions for your Supporting Information files at the end of your manuscript, and update any in-text citations to match accordingly. Please see our Supporting Information guidelines for more information: http://journals.plos.org/plosone/s/supporting-information. [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: 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: Yes 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: The authors conducted a retrospective cohort study for adult access to cardiology department in order to identify the leading cause of heart disease in this population Interestingly, heart failure represented a substantial burden of hospitalizations and the most common etiologies were chronic pulmonary heart disease with former mine workers and people with a history of TB being more likely to have a chronic pulmonary heart disease In order to tackle this health problem, the authors underline how it is paramount importance to understand the etiologies and risk factors for heart diseases and heart failure in the region. Moreover, the high number of chronic pulmonary heart diseases is striking and it is relevant how more research is warranted in this area. The definitions of hypertrophic cardiomyopathy and dilated cardiomiopathy aren’t correct. A clinical diagnosis of HCM in adult patients can therefore be established by imaging with 2D echocardiography or cardiovascular magnetic resonance (CMR) showing a maximal end-diastolic wall thickness of ≥15 mm anywhere in the left ventricle, in the absence of another cause of hypertrophy in adults (https://doi.org/10.1161/CIR.0000000000000937) Dilated Cardiomyopathy is defined as presence of left ventricular dilatation and left ventricular systolic dysfunction in the absence of abnormal loading conditions (hypertension and valve disease) or coronary artery disease sufficient to cause global systolic impairment (J Am Soc Echocardiogr 2015;28:1-39) Reviewer #2: I read with pleasure the manuscript “Etiology, characteristics and occurrence of heart diseases in rural Lesotho (ECHO-Lesotho): a retrospective echocardiography cohort study”, which aims to examine the occurrence, etiology and characteristics of heart diseases in Lesotho analyzing the echocardiographic data of a referral hospital. The study is very interesting because currently in the literature there are no data on heart diseases in Lesotho and, taking into account that cardiovascular diseases are becoming a major cause of death in Sub-Saharan Africa, it is important that they are investigated. However, I have to point out some issues that, in my opinion, need to be changed in order to accept and publish the scientific article: - The study has a major limitation regarding the small number of patients. The data collected from January 2020 to May 2021 are not sufficient to describe the situation of heart diseases in an African State. Data collection should be extended retrospectively as much as possible or, if the echocardiographic laboratory was recently established, it could be useful to combine the data with those of another hospital in Lesotho. - All the data collected with the echocardiogram were carefully described in the section “Echocardiography”, as well as the techniques used, but none of these data were reported in the manuscript. I don’t think it is necessary to describe these data so accurately for the purposes of the study that is being carried out and especially if they should not be included in the scientific article. - In the section “Definitions”, it would be interesting to insert the guideline or bibliographic reference for each definition. - In the table 1 there are incorrect numbers: the sum of females (n. 134) and males (n.84) with abnormal echocardiogram is 218 instead of 210, the sum of females (n. 87) and males (n. 30) with normal echocardiogram is 117 instead of 125. - In addition, in the table 1 it is also necessary to specify the different type of congenital heart disease diagnoses in the children with an abnormal echocardiogram. - In the section “Heart disease: Occurrence, characteristics and etiology”, is the sentence “of whom the majority (130/210; 64%) were female with a median age of 58 (interquartile range [IQR] 46-72) years old” correct? The data does not match with the data of table 1. - In the section “Heart failure: Occurrence, characteristics and etiology”, is the sentence “the majority of patients hospitalized due to heart failure were female (56%; 70/126) and had a median age of 66 years old (IQR 54-76)” correct? The data does not match with the data of table 2. - In the table 2 it would be better to divide the section of cardiovascular risk, the section of symptoms and the section of vital signs for greater clarity. - In the supplement table 1, the sum of percentages in section LV size, LV systolic function, diastolic relaxation impairment of LV is 101% instead 100%. - In addition, in the supplement table 1, regarding the LV systolic function and in particular the mild systolic heart failure, replace “LVEF 41-53%” with “LVEF 41-54%”. - In the line 263 “table 3” should be changed with “supplement table 1”. - During hospitalization for heart failure, which was the mean length of stay? Have there been any cardiovascular death and which were the causes? Could you add this additional data in the article? ****** 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.0278406.r001
Revision 1
1 Aug 2022 Author Response Find the well-formatted response letter uploaded separately. Response to Reviewers Etiology, characteristics and occurrence of heart diseases in rural Lesotho (ECHO-Lesotho): A retrospective echocardiography cohort study 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. Response: We updated our manuscript to meet PLOS ONE’s style requirements 2. We note that the grant information you provided in the ‘Funding Information’ and ‘Financial Disclosure’ sections do not match. When you resubmit, please ensure that you provide the correct grant numbers for the awards you received for your study in the ‘Funding Information’ section. Response: We updated our funding information and provided the grant number in the in all relevant sections 3. We note that you have stated that you will provide repository information for your data at acceptance. Should your manuscript be accepted for publication, we will hold it until you provide the relevant accession numbers or DOIs necessary to access your data. If you wish to make changes to your Data Availability statement, please describe these changes in your cover letter and we will update your Data Availability statement to reflect the information you provide. Response: We are already preparing the anonymized dataset for upload onto Zenodo and will be ready with DOI in time. 4. Please include captions for your Supporting Information files at the end of your manuscript, and update any in-text citations to match accordingly. Please see our Supporting Information guidelines for more information: http://journals.plos.org/plosone/s/supporting-information. Response: We updated our manuscript to meet PLOS ONE’s style requirements Reviewer #1: 1. The definitions of hypertrophic cardiomyopathy and dilated cardiomiopathy aren’t correct. A clinical diagnosis of HCM in adult patients can therefore be established by imaging with 2D echocardiography or cardiovascular magnetic resonance (CMR) showing a maximal end-diastolic wall thickness of ≥15 mm anywhere in the left ventricle, in the absence of another cause of hypertrophy in adults (https://doi.org/10.1161/CIR.0000000000000937). Dilated Cardiomyopathy is defined as presence of left ventricular dilatation and left ventricular systolic dysfunction in the absence of abnormal loading conditions (hypertension and valve disease) or coronary artery disease sufficient to cause global systolic impairment (J Am Soc Echocardiogr 2015;28:1-39) Response: Thank you very much for spotting this important error from our side. We realized that there was a misunderstanding between the writing and the clinical team and the definitions for HCM and DCM were not correctly reflected. We adapted the definitions, added the corresponding guideline references and these were the definitions used by the clinical team during examination. We adapted accordingly in section “Definitions”: Dilated cardiomyopathy. “LV or biventricular dilation and impaired contraction, not explained by abnormal loading conditions (e.g. hypertension and valvular heart disease) or coronary artery disease” Hypertrophic cardiomyopathy. “A maximal end-diastolic wall thickness of ≥15 mm anywhere in the LV, in the absence of another cause of hypertrophy” Reviewer #2: 1. I read with pleasure the manuscript “Etiology, characteristics and occurrence of heart diseases in rural Lesotho (ECHO-Lesotho): a retrospective echocardiography cohort study”, which aims to examine the occurrence, etiology and characteristics of heart diseases in Lesotho analyzing the echocardiographic data of a referral hospital. The study is very interesting because currently in the literature there are no data on heart diseases in Lesotho and, taking into account that cardiovascular diseases are becoming a major cause of death in Sub-Saharan Africa, it is important that they are investigated. Response: Thank you very much for your positive feedback. 2. However, I have to point out some issues that, in my opinion, need to be changed in order to accept and publish the scientific article: The study has a major limitation regarding the small number of patients. The data collected from January 2020 to May 2021 are not sufficient to describe the situation of heart diseases in an African State. Data collection should be extended retrospectively as much as possible, or, if the echocardiographic laboratory was recently established, it could be useful to combine the data with those of another hospital in Lesotho. Response: We agree with the reviewer that the data is limited. The echocardiography department was established in January 2020 (mentioned in the manuscript). The only other health facility in Lesotho that has an echocardiography department is in the capital, in Maseru. During the implementation of the echocardiography department, we were in contact with that hospital, however, they did not agree to share their data. We are planning to conduct an update of our data, but since there was a change of leadership in mid-2021 it became more difficult to collaborate. Despite these shortcomings, we believe that it is important to get this data out into the public – to at least have some initial data from Lesotho – and to stimulate more research about this topic in the country. 3. All the data collected with the echocardiogram were carefully described in the section “Echocardiography”, as well as the techniques used, but none of these data were reported in the manuscript. I don’t think it is necessary to describe these data so accurately for the purposes of the study that is being carried out and especially if they should not be included in the scientific article. Response: We think that these details are important for two reasons. First, these details help to understand the echocardiography definitions we used and the results presented (Supporting Information S1 Table provides the details). Second, we think these details are crucial in case someone wants to reproduce our study findings. However, we understand the reviewers concern and think this paragraph is too prominent in the main manuscript. Thus, we moved this entire paragraph into the Supporting Information (S1 Text) and added a sentence in section “Definitions”: “We provide detailed information about the echocardiography machine, techniques and measurements used in S1 Text.” 4. In the section “Definitions”, it would be interesting to insert the guideline or bibliographic reference for each definition. Response: We added the respective guideline/reference for each definition. 5. In the table 1 there are incorrect numbers: the sum of females (n. 134) and males (n.84) with abnormal echocardiogram is 218 instead of 210, the sum of females (n. 87) and males (n. 30) with normal echocardiogram is 117 instead of 125. Response: Thank you for pointing out this important typo. We corrected the numbers. 6. In addition, in the table 1 it is also necessary to specify the different type of congenital heart disease diagnoses in the children with an abnormal echocardiogram. Response: We added the details of these 3 congenital heart diseases in the footnote of Table 1: “[1] Congenital heart diseases: 1 girl with an aortic stenosis (bicuspid aortic valve) and 1 girl and 1 boy with a patent ductus arteriosus” 7. In the section “Heart disease: Occurrence, characteristics and etiology”, is the sentence “of whom the majority (130/210; 64%) were female with a median age of 58 (interquartile range [IQR] 46-72) years old” correct? The data does not match with the data of table 1. Response: Thank you for spotting this typo. It was related to the above typo and the median age was wrongly taken from the overall population instead of only the population with abnormal echocardiogram. We corrected the numbers. 8. In the section “Heart failure: Occurrence, characteristics and etiology”, is the sentence “the majority of patients hospitalized due to heart failure were female (56%; 70/126) and had a median age of 66 years old (IQR 54-76)” correct? The data does not match with the data of table 2. Response: This is correct and matches the data of table 2. There were a total of 126 hospitalized patients due to heart failure (Total in first column), they had a median age of 66 years with an IQR 54-76 (median age in first column) and 56% were female (n=70/126, third column). 9. In the table 2 it would be better to divide the section of cardiovascular risk, the section of symptoms and the section of vital signs for greater clarity. Response: We thank the reviewer for this great suggestion and adapted accordingly. 10. In the supplement table 1, the sum of percentages in section LV size, LV systolic function, diastolic relaxation impairment of LV is 101% instead 100%. Response: This was due to rounding. We added one decimal digit everywhere to avoid misleading sums due to rounding. 11. In addition, in the supplement table 1, regarding the LV systolic function and in particular the mild systolic heart failure, replace “LVEF 41-53%” with “LVEF 41-54%”. Response: Thank you for spotting this. The mistake was not adding a ‘greater than or equal sign’ in front of LVEF 54%. We corrected accordingly to “LVEF ≥ 54%”. 12. In the line 263 “table 3” should be changed with “supplement table 1”. Response: We adapted accordingly. 13. During hospitalization for heart failure, which was the mean length of stay? Have there been any cardiovascular death and which were the causes? Could you add this additional data in the article? Response: Unfortunately, our retrospective data collection tool did not include length of hospitalization. However, we do have the mortality data. We added a short paragraph just before section “Heart failure: risk factors for the most common heart failure etiology” to summarize this data: “4 patients died during the hospitalization: A 70 years old male with chronic pulmonary heart disease, a 18 years old male with a fulminant acute pulmonary heart disease, a 56 years old female with dilated cardiomyopathy and a 51 years old female with a valvular (rheumatic) heart disease.” Attachments Attachment Submitted filename: ECHO_response_to_reviewers.docx https://doi.org/10.1371/journal.pone.0278406.r002
16 Nov 2022 Decision Letter - Roberto Magalhães Saraiva, Editor Etiology, characteristics and occurrence of heart diseases in rural Lesotho (ECHO-Lesotho): A retrospective echocardiography cohort study PONE-D-21-39404R1 Dear Dr. Amstutz, 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, Roberto Magalhães Saraiva, MD, 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 ******** 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 ****** 3. Has the statistical analysis been performed appropriately and rigorously? 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 #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 #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 #2: I read the reviewed version of the article “Etiology, characteristics and occurrence of heart diseases in rural Lesotho (ECHO-Lesotho): a retrospective echocardiography cohort study”, a retrospective cohort study which treats etiology, characteristics and occurrence of heart disease in Lesotho analyzing data from an echocardiography department. The comments raised in the previous review have been addressed as far as possible and, in my opinion, now this manuscript is acceptable for publication, aware of the fact that the small number of patients cannot fully represent the situation of heart disease in an African State. Maybe the article title should be changed to “a preview of a retrospective echocardiography cohort study” hinting at the intention to continue the study increasing the number of patients. ****** 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 ******** https://doi.org/10.1371/journal.pone.0278406.r003
Formally Accepted
7 Dec 2022 Acceptance Letter - Roberto Magalhães Saraiva, Editor PONE-D-21-39404R1 Etiology, characteristics and occurrence of heart diseases in rural Lesotho (ECHO-Lesotho): A retrospective echocardiography cohort study Dear Dr. Amstutz: 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. Roberto Magalhães Saraiva Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0278406.r004

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