-->PONE-D-26-09243-->-->Awareness, attitudes, and barriers toward Transthyretin Amyloid Cardiomyopathy in Latin America: A questionnaire-based cross-sectional study-->-->PLOS One

Dear Dr. Silva Julian,

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Academic Editor

PLOS One

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Reviewers' comments:

Reviewer's Responses to Questions

-->Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. -->

Reviewer #1: Yes

Reviewer #2: Yes

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

Reviewer #1: No

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: No

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: No

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: This manuscript presents a cross-sectional, questionnaire-based study assessing awareness, attitudes, and perceived barriers related to transthyretin amyloid cardiomyopathy (ATTR-CM) among physicians across multiple Latin American countries. The study addresses an important and underexplored topic, given the challenges associated with the recognition, diagnosis, and management of ATTR-CM in real-world clinical settings, particularly in regions with heterogeneous healthcare systems. By collecting data from a relatively large and diverse sample of healthcare professionals, the authors provide insights into current clinical practices, identify gaps in knowledge and access to diagnostic tools and treatments, and highlight potential areas for improvement in patient care. Overall, the study contributes valuable regional data that may help inform future educational strategies and healthcare planning initiatives.

However, the manuscript has significant methodological, reporting, and clarity issues that currently limit its scientific robustness and interpretability.

Minor revisions:

- “Amyloidosis Cardiomyopathy (ATTR-CA)” is incorrect. The correct term is “Transthyretin Amyloid Cardiomyopathy,” with the abbreviation ATTR-CM. Please revise this throughout the manuscript.

- In line 105, in addition to reference 7, the recent review article describing all identified mutations in the TTR gene should be included (DOI: 10.1080/10408363.2024.2350379).

- In line 123, according to the Amyloid Nomenclature 2024 (DOI: 10.1080/13506129.2024.2405948), the abbreviation for wild-type transthyretin amyloidosis should be TTRwt, and for hereditary ATTR amyloidosis, ATTRv. Please revise accordingly.

- In line 206, “CARI” is used without definition and should be defined at first mention.

Major revisions:

1) The authors should consider providing the full questionnaire as supplementary material to enhance transparency and facilitate the assessment of the study instrument.

2) The manuscript would benefit from adherence to the STROBE guidelines for cross-sectional studies, which would strengthen the transparency, completeness, and overall quality of reporting.

3) The statistical analysis also requires clearer justification and description. Although the study is presented as primarily descriptive, the inclusion of inferential analyses (e.g., ANOVA and multivariate approaches) suggests a more analytical framework. Clarifying the rationale for these analyses, the variables included in the models, and whether any adjustments for multiple comparisons were performed would strengthen the methodological rigor.

4) The authors state that formal approval from an institutional review board or independent ethics committee was not required due to the nature of the study. However, the authors also indicate that the study was conducted in accordance with the Declaration of Helsinki, which explicitly requires prior review by an independent ethics committee for studies involving human participants. Therefore, it would be helpful to clarify how these statements should be reconciled.

5) A more in-depth analysis of how the findings can be translated into concrete clinical or policy interventions would increase the practical relevance of the study. For example, detailing how the identified knowledge and access gaps could guide targeted educational initiatives, diagnostic flows, or improvements to each country's healthcare system would add value to the discussion.

6) Figure 1 appears to be of low resolution, which makes several elements difficult to read and limits the interpretation of the presented data. The authors are encouraged to provide a higher-resolution version of this figure.

7) Some conclusions appear to overstate the level of awareness and should be more closely aligned with the descriptive nature of the data. For example, statements suggesting “moderate to high awareness” in certain countries (e.g., Brazil and Mexico) are not fully supported by the reported findings, where a substantial proportion of physicians still report limited knowledge of ATTR-CM. Similarly, while the study identifies variability in diagnostic practices and access to tools, the conclusions sometimes imply a higher level of clinical preparedness than the results suggest, particularly given that a large proportion of respondents reported managing few or no patients with ATTR-CM in the past year. Therefore, the authors are encouraged to ensure that the conclusions more strictly reflect the descriptive and self-reported nature of the survey data.

8) The manuscript would benefit from careful revision of the English language. While the overall content is understandable, there are some grammatical mistakes. A thorough language editing is widely recommended.

Reviewer #2: This paper reports the results of an online cross sectional survey of internal medicine, cardiology and neurology physicians managing cardiac amyloidosis conducted in 8 latin american countries. The results indicate substantial knowledge gaps, lack of resourcces, delay in diagnosis , and heterogeneity of management of the condition.

The data are original but of limited novelty since the concept has been shown in other countries including the US. These data are probably of limited interest to the broader readership beyond Latin America.

The methodology is valid, but more details are needed on how physicians were made aware of survey and who responded, to understand the inevitable biases inherent in such studies. The conclusion are forthcoming from the data they present. There are some typos, but overall the manuscript is presented well and easy to read.

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Reviewer #1: No

Reviewer #2: No

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Awareness, attitudes, and barriers toward Transthyretin Amyloid Cardiomyopathy in Latin America: A questionnaire-based cross-sectional study

PONE-D-26-09243R1

Dear Dr. Silva Julian,

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.

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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 #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

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-->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

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-->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: (No Response)

Reviewer #2: (No Response)

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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

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