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. 2024 Mar 11;19(3):e0292694. doi: 10.1371/journal.pone.0292694

Two–Dimensional and Doppler trans-thoracic echocardiographic patterns of suspected pediatric heart diseases at Tibebe-—Ghion specialized Teaching Hospital and Adinas General Hospital, Bahir Dar, North-west Ethiopia:–An experience from an LMIC

Tesfaye Taye Gelaw 1,*, Amare Aschalew Yehuala 1, Senay Zerihun Mengste 1, Yalemwork Anteneh Yimer 1, Habtamu Bayih Engida 2, Abiot Tefera Alem 2
Editor: Endale Tefera3
PMCID: PMC10927071  PMID: 38466681

Abstract

Background

Transthoracic Echocardiography is the first-line, non-invasive, and accessible imaging modality to evaluate heart disease anatomy, physiology, and hemodynamics. We aim to describe the trans-thoracic echocardiography pattern of pediatric heart diseases and reasons for referral in children referred to Bahir Dar University Tibebe–Ghion Hospital and Adinas General Hospital.

Method

A descriptive cross-sectional study of the archived Transthoracic, Two Dimensional, and Doppler Echocardiography assessments of children from birth to fifteen years of age performed between June 2019 to May 2023 was done. Data were collected retrospectively from February 01, 2023 –May 31, 2023. Categorical variables like gender, referral reasons for echocardiography, and patterns of pediatric heart lesions were analyzed in the form of proportions and presented in tables and figures. Discrete variables including age were summarized as means (SD) and medians(IQR).

Results

Out of 3,647 Children enrolled; 1,917 (52.6%) were males and 1,730 (47.4%) were females. The median (IQR) age of children enrolled was 24 months (5 to 96). Cardiac murmur (33%) was the most common reason for echocardiography followed by, Respiratory Distress (18%), Syndromic Child (15%), easy fatigability/ Diaphoresis (14.3%), congestive heart failure (14%), and rheumatic fever (13.2%). Congenital heart defect (CHD) accounts for 70% of all heart diseases, followed by rheumatic heart disease (21%). Isolated ventricular septal defect(VSD) was the most common CHD (21%) followed by isolated Patent ductus arteriosus (15%), isolated atrial septal defect (10%), Isolated atrioventricular septal defect (6%) and isolated pulmonary stenosis (5%). Cyanotic CHD accounts for 11.5% of all heart diseases. Tetralogy of Fallot (30%), d-TGA (20%), and double outlet right ventricle (19%) were the most common cyanotic CHDs.

Conclusions

In our study, congenital heart lesions are the most common diagnosis and cardiac murmurs are the most common presenting reasons for echocardiography evaluation.

Introduction

According to the WHO Report, across all age groups; Cardiovascular diseases account for the most Non-Communicable Disease (NCD) deaths, or 17.9 million people annually [1]. With the United Nations’ adoption of the Sustainable Development Goals; specifically Sustainable Development Goal 3.2, that aims to end preventable deaths of newborns and children under 5 years of age, a significant reduction has been achieved in global mortality from communicable disease [2, 3].

It is notable that Pediatric Heart diseases including Congenital Heart Diseases (CHD) and acquired heart diseases (AHD), which affect a significant number of children, have largely been left untouched in Low–and Middle–low-income countries in contrary to SDG 3.4, which aims to reduce by one-third premature mortality from non-communicable diseases [4]. Unorganized referral system, treatment and follow-up gaps; and Lack of availability of diagnostic equipment, infrastructure, and trained personnel are some of the main barriers to providing quality Pediatric Heart Disease care in low–and Middle–middle-income countries [5]. Therefore, Screening, Detection, and treatment of NCDs, including Heart diseases, are key components of the response to NCDs [1].

Transthoracic Echocardiography is the first-line, non-invasive, portable, and accessible imaging modality in the diagnosis and evaluation of pediatric heart disease anatomy, physiology, and hemodynamics [6–10]. Given the increasing cost of healthcare and limited human power, it is essential to ensure that the use of cardiovascular imaging is appropriate [11].

Reasons for Pediatric echocardiogram encompass a wide range of clinical conditions. These include: respiratory distress, congestive heart failure, cyanosis, exertional chest pain, syncope, failure to thrive, murmurs, cardiomegaly, Infective endocarditis, rheumatic fever, thrombo-embolic events, arrhythmia, systemic hypertension, pulmonary hypertension, syndromes associated with cardiovascular disease, cardiogenic shock, heart surgery, and Fetal echocardiography [6, 12–17].

So far, there is limited information regarding echocardiographic patterns and the reason for referral for echocardiography of suspected pediatric cardiac patients with such a larger number in Ethiopia [18]. Having such a piece of descriptive detailed information from a tertiary health care facility would provide very relevant information to further study the pattern and nature of pediatric heart diseases in other corners of the country. It also will complement the available information on pediatric echocardiographic studies at the global level from the LMIC’s side.

Cognizant of this, we undertook a retrospective review of four-year archived Trans-Thoracic echocardiography done using the segmental analysis approach for Pediatric patients referred for echocardiography to the cardiac care units. This study will help to define the pattern of Pediatric cardiac disease in our community, and further add to the national and global database.

Method

Setting and participants

The study was conducted on 3,647 pediatric clients with complete documentation and no previous echocardiography assessment who were referred to the Paediatric Echocardiography laboratories of Adinas General Hospital; a privately owned Hospital and Bahir Dar University Tibebe-Ghion Teaching Hospital, from June 2019 to May 2023. The Hospitals serve as referral centers for pediatric cardiac diagnostics and medical treatment for Northwest and part of West Ethiopia. Part of the clients who are residing near these two hospitals were being cared for in the respective hospitals and the rest majority were being referred back to the referring health institutes with complements for follow-up and medical management in their vicinity. Only a few of them were referred to a center where surgical and transcatheter interventions are available due to economic reasons. Data were collected from February 01, 2023 –May 31, 2023, on a retrospective basis from the archives of the respective Hospitals’. An echocardiography study was performed by a pediatric Cardiologist and doubtful findings were discussed amongst the cardiologists before writing an official report. Data were collected by Trained Pediatricians and adult and pediatric Cardiologists.

Study tool

Phillips iE33 xMATRIX model ultrasound system echocardiography was used for collecting echocardiographic data from Bahir Dar University Tibebe-Ghion Hospital and the GE LOGIQ C5 Premium model was used for echocardiographic data collection from Adinas General Hospital. 2D echocardiography and Doppler with all cardiac measurements were taken. Echocardiography evaluation was made using the segmental sequential analysis [8].

Study design

Descriptive cross-sectional analysis of all archived completely documented echocardiography assessment reports done using sequential segmental analysis was done [6, 19–21]. Descriptive analysis was performed for age, gender, reasons for referral for echocardiography, and echocardiographic diagnoses. Ethical clearance and waiver of consent were obtained from the ethics and research committee of the College of Medicine and Health Sciences of Bahir Dar University with protocol number: 795/2023.

Diagnosis and classification

Clinically suspected Myocarditis [22–24]

Acute: A poorly functioning ventricle with or without dilation, recent heart failure symptoms, and viral infectious symptoms in the preceding weeks.

Fulminant: Presents as a cardiogenic shock; tachyarrhythmias are common, and inotropic or mechanical circulatory support (MCS) may be needed.

Cardiomyopathy [25, 26]: Structural and functional abnormalities of the ventricular myocardium that are unexplained by flow-limiting coronary artery disease or abnormal loading conditions.

Primary: The heart is the only involved organ. Can be Genetic, Non-Genetic, or Acquired.

Secondary: A manifestation of a systemic disorder. shows pathological myocardial involvement as part of a large number and variety of generalized systemic disorders.

Statistical analysis

Recorded data was cleared, coded, and entered into SPSS version 25 for analysis. Categorical variables including gender, reasons for referral for echocardiography, and diagnostic patterns of pediatric heart lesions were analyzed in the form of proportions and percentages and presented in tables and figures. Discrete variables including age were analyzed and summarized as means (SD) and medians (IQR).

Result

3,672 Pediatric clients suspected of cardiac lesions visited Bahir Dar University Tibebe–Ghion Hospital and Adinas General Hospital echocardiography Laboratories for the first time from June 2019 –to May 2023. Of which twenty-five were excluded because of incomplete documentation and the remaining 3,647 were subjected to analysis (Fig 1).

Fig 1. Echocardiography study flow diagram: Bahir Dar University Tibebe-Ghion and Adinas Hospitals, June 2019—May 2023.

Fig 1

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PPHTN = Persistent Pulmonary Hypertension of the newborn. PHT = Pulmonary Hypertension. CHD = Congenital Heart Diseases. DCM = Cardiomyopathy. RHD = Rheumatic Heart Diseases.

Out of the 3,647 Pediatric echocardiography first-time assessments with complete documentation; 501 (13.7%) were neonates, 916 (25.1%) were infants, 389 (10.7%) were toddlers, 627 (17.2%) were preschoolers, 761 (20.9%) were school age, and 453 (12.4%) were adolescents. The median (IQR) age of children subjected to the study was 24 (5–96) months. There were 1,917 (52.6%) males and 1,730 (47.4%) females, making a male-to-female ratio of 1.1:1.

The most common reason for referral for echocardiography was cardiac murmur (33%) followed by Respiratory Distress (18%), Syndromic Child (15%), easy fatigability (14.3%), Congestive Heart Failure (14%), Rheumatic Fever (acute & recurrent) (13.2%), dyspnea on exertion (7.5%), recurrent chest infection (7%), cyanosis (5.8%), palpitation (5.6%), and Others (Fig 2.).

Fig 2. Reasons for referral for echocardiography: Bahir Dar University Tibebe-Ghion and Adinas Hospitals, June 2019—May 2023.

Fig 2

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Out of the 3, 647 pediatric clients with complete documentation and first-time visits; 2,273 children had one or more cardiac lesions on echocardiography, reflecting the proportion of children identified with cardiac lesions to be 62%. The remaining 38% were found to be normal while having one or more of the clinical manifestations of cardiac lesions as a reason for referral. All children presenting with cyanosis, clubbing, Pericardial friction rub, and thrombo-embolic events had cardiac lesions identified using echocardiography evaluation; whereas pediatric clients whose reason for referral was being infant of diabetic mother (16.7%), Syncope (18.2%), suspected Persistent pulmonary Hypertension of the newborn (19.4%), recurrent chest infection (19.8%), congenital stridor (20%) and non–selective Pre-Operative screening (21.2%) were having lower proportion of heart lesions to uncover any cardiac abnormalities (S1 Table).

Congenital heart defects (CHDs) account for 1597(70%) of all Pediatric Heart diseases; followed by rheumatic heart diseases, 479(21%); Pulmonary hypertension not caused by left side heart failure, 79(3.5%); Pericardial diseases, 51(2.2%); all forms of cardiomyopathies, 52(2.3%); and clinically suspected myocarditis, 28(1.2%). Isolated ventricular septal defect(VSD) was the most common CHD (21%) followed by isolated Patent ductus arteriosus (15%), isolated atrial septal defect (10%), Isolated atrioventricular septal defect (6%) and isolated pulmonary stenosis (5%). Tetralogy of Fallot is the leading cyanotic congenital heart defect accounting for 3.4% of all heart diseases (4.9% of all CHDs and 30% of all cyanotic CHDs) followed by d-TGA (2.2% of all heart diseases, 3.3% of all CHDs and 19.5% of all cyanotic CHDs), and double outlet right ventricle (2.2% of all heart diseases, 3% of all CHDs and 19% of all cyanotic CHDs) (Table 1).

Table 1. Relative frequency of paediatric heart diseases: Tibebe-Ghion and Adinas Hospitals, June 2019 –May 2023.

0–28 days 1–12 months ≥1–2 years ≥2–6 years ≥6–12 years ≥12–18 years Total Percent
Acyanotic CHDs, Isolated 241 461 184 229 119 61 1295 57
    Isolated ASD 47 47 18 22 14 10 158 12.2
    Isolated VSD 36 122 54 68 35 15 330 25.5
    Isolated AVSD 9 44 17 16 7 3 96 7.4
    Isolated PDA 50 79 37 44 17 7 234 18.1
    Isolated Pulmonary Stenosis 10 31 13 17 8 4 83 6.4
    Two or more combined acyanotic CHDs 75 124 38 49 26 8 320 24.7
    Ebstein anomaly of Tricuspid valve 3 1 0 2 2 4 12 0.9
    Other acyanotic CHDs 11 13 7 11 10 10 62 4.8
Minor CHD + Severe PHT 0 13 6 1 0 1 21 0.9
Acyanotic CHD + Acquired heart disease 0 1 1 2 4 0 8 0.35
S/P Surgical or device intervention 0 0 1 5 4 0 10 0.4
PHT, (Isolated + PPHTN) 9 15 12 16 2 4 58 2.55
Cyanotic Congenital heart defects 37 103 34 54 23 10 261 11.5
    Tetralogy of Fallot 7 23 12 17 13 6 78 29.9
    d-TGA 11 23 4 10 3 0 51 19.5
        d-TGA + Intact IVS/Restrictive VSD 3 9 0 0 0 0 12
        d- TGA + adequate mixing 7 9 3 8 1 0 28
        d-TGA + VSD + LVOTO 1 5 1 2 2 0 11
    Double Outlet Right Ventricle/DORV/ 6 22 9 9 1 2 49 18.8
        DORV—VSD type 0 7 4 2 1 0 14
        DORV-TOF type 1 1 1 2 0 1 6
        DORV-TGA type 0 4 0 0 0 0 4
        DORV with Non-committed VSD 3 5 3 2 0 1 14
        DORV-AVSD-PS-Hetrotaxy 2 4 1 2 0 0 9
        DORV with no VSD 0 1 0 1 0 0 2
    Double Outlet Left Ventricle 2 0 1 0 2 1 6 2.3
    Tricuspid Atresia 5 15 3 6 2 31 11.9
    Truncus Arteriosus 2 8 2 5 2 19 7.3
    Hypoplastic Left Heart Syndrome 2 8 0 0 0 10 3.8
    Mitral atresia 1 2 1 3 0 7 2.7
    Other cyanotic CHDs 1 2 2 3 0 1 9 3.4
    S/P Arterial switch operation 0 0 0 1 0 0 1 0.4
Acquired Heart Diseases 2 24 16 79 274 225 620 27.3
    Rheumatic Heart Diseases 0 0 0 45 240 189 474 76.5
    Myocarditis 1 11 5 5 4 1 27 4.4
    Cardiomyopathies 1 10 7 14 10 8 50 8
    Pericardial Diseases 0 2 4 10 17 18 51 8.2
    Other Acquired Heart Diseases 0 1 0 5 3 8 17 2.7
    S/P MV Commissurotomy 0 0 0 0 0 1 1 0.2
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Discussion

Our study shows very important information regarding the reasons for referral, trends, and patterns of heart diseases in children. Among children referred for echocardiography, 62% had heart lesions which is in line with an Indian study [27]. In our study, the most commonly reported reason for referral for echocardiography is detecting murmur on clinical evaluation (33%) as reported in different parts of the world [28, 29]. This finding provides insight into the various reasons for referral for echocardiography evaluation provided by all categories of health care providers. It also encourages healthcare providers to advocate and practice routine clinical evaluation of children during a scheduled or unscheduled health service visit.

Our study also showed that infants from one to twelve months of age have the highest proportion of heart defects compared to the other age groups (27.1%). According to Zimmerman’s work on CHDs in low-and-middle-income countries, it is more common for children to present in later stages of the disease and at older ages in low-resource settings [30]. This might be, in part, explained by delayed presentation and diagnosis fueled by an unorganized referral system, a lower level of awareness and health-seeking behavior; and a Lack of availability of diagnostic equipment, infrastructure, and trained personnel in the vicinity. In addition, newborns with critical CHD may be misdiagnosed or may not make it to the hospital and die at home or somewhere else which in turn will decrease the proportion of newborns with CHD in our study.

Congenital heart defect is the most common heart lesion in our study. This finding is not in line with what was previously thought about the proportion of congenital heart defects in low- and middle-income countries [31, 32]. The possible explanation is that, though incidence and prevalence can be affected by genetic and environmental factors, there is no strong clue that CHDs are less in LMICs compared to HICs. In addition, the scarcity of diagnostic services in the former days in these regions has led to undermining the caseload and possible misdiagnosis.

The most common congenital heart defect identified in our study is isolated ventricular septal defect followed by isolated patent ductus arteriosus and isolated atrial septal defect respectively. This is similar to most other studies done in both developed and developing countries except for the Iranian and Nigerian studies that reflect atrial septal defect is the most common one [28, 29, 33–39]. This difference from the Iranian and Nigerian studies is possible because children with atrial septal defects are asymptomatic and hence are less likely to show to health institutes with clinical features of heart diseases, unlike children who were screened at school and in the community like in the case of the Nigerian study. The Iranian study focused only on neonates in whom small atrial septal defects are expected to close and decrease the proportion of the defect in later ages and lack generalizability [39, 40].

In our study, Tetralogy of Fallot is the leading cyanotic congenital heart defect followed by d-TGA, and double outlet right ventricle respectively. These findings are consistent with studies done in other sites [41–44]. Ventricular septal defect and tetralogy of Fallot were the most common acyanotic and cyanotic lesions, respectively. These findings are similar to studies done elsewhere [28, 32, 36, 43].

Rheumatic heart disease is the leading acquired heart disease in our study followed by cardiomyopathies and/or clinically Suspected Myocarditis and Pericardial diseases respectively. This finding is similar to studies done in Nigeria and other global data in general [31, 45]. Other data from the USA and Japanese community showed the most common acquired heart disease to be Kawasaki Disease [46]. This difference may be explained by environmental, genetic, and socio-cultural differences. We also had children with both CHD and acquired heart diseases. These clients were evaluated rigorously to substantiate their diagnosis using operational definitions. Diagnosing acquired heart disease while the child is having a congenital heart lesion is challenging as there are no clear criteria set to diagnose such conditions in children.

Conclusion

Congenital heart defects were the most common echocardiographic diagnosis, and the presence of a murmur was the most common reason for referral for echocardiography assessment. VSD, PDA, and ASD were the most common acyanotic heart defects while Tetralogy of Fallot and Double outlet right ventricle topped the cyanotic defects.

Limitations

This study is a descriptive retrospective institutional study. Hence, generalizability is limited as it doesn’t represent the whole population and is only descriptive. This study also doesn’t address the appropriateness of “not performing” echocardiography; given children are presented to the respective units for echocardiography assessment. Diagnosing CHDs combined with acquired heart diseases using transthoracic echocardiography in children has no set criteria so far inciting the need for future work.

Recommendations

Additional studies are warranted to further define the pattern of pediatric cardiac disease in our environment, and add relevant information to the national and global database representing LMICs.

Supporting information

S1 Table. Proportion of children with 1.

(DOCX)

pone.0292694.s001.docx (17.7KB, docx)
S1 File

(ZIP)

pone.0292694.s002.zip (6.5MB, zip)
S2 File

(ZIP)

pone.0292694.s003.zip (8.7MB, zip)

Acknowledgments

We thank the Pediatric and Child health residents and Clinical nurses at the cardiac unit of Bahir Dar University Tibebe–Ghion Hospital for their relentless support of the pediatric cardiac services being provided at the unit. Our thanks also go to the Administration and Radiology Unit of Adinas General Hospital for providing uswith the necessary documents.

Abbreviations

ASD

Atrial septal defect

AVSD

Atrioventricular septal defect

CHD

Congenital Heart Defect

DORV

Double outlet right ventricle

LVOTO

Left ventricular outflow tract obstruction

MV

Mitral valve

PDA

Patent ductus arteriosus

PHT

Pulmonary Hypertension

PPHTN

Persistent Pulmonary Hypertension of the newborn

PS

Pulmonary stenosis

TGA

Transposition of great arteries

TOF

Tetralogy of Fallot

VSD

Ventricular septal defect

Data Availability

All relevant data are within the manuscript and its Supporting Information files.

Funding Statement

The author(s) received no specific funding for this work.

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Decision Letter 0

Endale Tefera

1 Dec 2023

PONE-D-23-28984Two – Dimensional and Doppler Transthoracic Echocardiographic Patterns of suspected Paediatric Heart Diseases at Tibebe – Ghion Specialized Teaching Hospital and Adinas General Hospital, Bahir Dar, North West Ethiopia: – an experience from a LMIC.PLOS ONE

Dear Dr. Gelaw,

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. Reviewers' comments are appended at the bottom of this email. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process. In my opinion, your manuscript should focus on a single clear objective. If you are reporting the spectrum of pediatric cardiac conditions you see in your practice, this should guide your methodology, results and discussion sections. If it's something else, it has to be spelled correctly. Additionally, presentation of results has to be concise and summarized. 

Please submit your revised manuscript by Jan 15 2024 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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We look forward to receiving your revised manuscript.

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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

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2. We noticed you have some minor occurrence of overlapping text with the following previous publication(s), which needs to be addressed:

- 10.1016/j.echo.2006.09.001

- 10.4103/jiae.jiae_60_20

In your revision ensure you cite all your sources (including your own works), and quote or rephrase any duplicated text outside the methods section. Further consideration is dependent on these concerns being addressed.

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.

4. We are unable to open your Supporting Information file [Echo Submited to PLOS ONE.rar]. Please kindly revise as necessary and re-upload.

[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

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

Reviewer #1: Yes

Reviewer #2: No

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3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: No

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4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: No

Reviewer #2: No

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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: Echocardiographic patterns

I would like to thank the authors for doing such a great job. I have the following comments/concerns:

Major concern:

- The aim of the study is not clear; is it to assess the “ Status of appropriate Use Criteria of Echocardiography in outpatient department of the study setting” or is it to determine “The magnitude of cardiac diseases among the screened pediatric patients in the study setting” or is it to assess “Correlation between clinical symptoms and echocardiographic covariates”. It is good if the authors can address only one of the above mentioned study aim since I saw authors using the above mentioned “aims” interchangeably in the manuscript.

Other comment:

- The title is lengthy.; better if you shorten it and also make it reflect the aim/finding of the study.

- There are punctuation errors and some grammar errors as well. E.g The authors are using the semicolon punctuation mark when they are listing items

Abstract Section:

- The result section in the abstract is too long.

- Conclusion in the abstract reads as “Indication based pediatric echocardiography has shown higher disease detection.” The basis of this conclusion is not clear. Which result does support such finding and what does it imply, does it mean the clinicians are following the “appropriate Use criteria”?

Introduction section:

- I recommend the authors either to remove or modify paragraph-4 on page-3 and paragraph -2 on page – 4 since they are not important to explain why the study is important.

- At the end of the introduction section the authors have stated that “..the study will help to define the pattern of pediatric cardiac disease…”. But in the abstract section, the authors stated “… we investigated indications for transthoracic echocardiography…”. Please be clear with aim of the study.

Methods section:

- It is good if the authors can provide information regarding data collection technique. E.g Were the data collected from the chart or from the saved video clips; who collected the data (physician, cardiologist….); who did the ECHO (cardiologist…), How was doubtful finding resolved….?

- Why the authors included post intervention cases in the study is not clear.

Result section:

- “3,672 clients had a visit to…” Does this mean all the pediatric patients who visited the hospital or…?

- I recommend the authors to remove some of the figures/tables so that the result section will be precise and concise in order to make it appealing for readers. For example, think about the importance of Table-2 and Table-3. Also, Table 4-2 appears that it is continuation of Table 4-1. The rows and columns of the two tables are too many and it is good if you can merge some variables and shorten it.

- It is good if the authors can cross-check the journal’s recommendation on how to write table headings.

- Title of Table -1 is not clear; what does “Diagnostic yield of TTE” means? To my understanding, diagnostic “yield of TTE” is the number of cardiac patients detected by the TEE and who subsequently proven to have the cardiac disease by other standard test divided by the total number of patients who underwent the screening. But Table-1 is not depicting such data.

Discussion section:

- I believe that the authors can improve the discussion section by focusing on the major findings of the study and the implication of the findings. As it stands right now, the discussion section mainly focuses on comparing prevalence values across different settings. That makes the discussion very superficial.

- For example, the authors have found out that screened infants have more prevalence of cardiac disease than other age groups. What does this imply? Is it because kids with cardiac disease die early? If so substantiate with evidence.

- Also, why CHD is more common than acquired heart disease among the screened population in a setting where RHD is assumed to be very prevalent?

- What does the 62% correlation between clinical suspicion of cardiac disease and ECHO finding of the disease indicate? Does it show the clinicians are good in assessing cardiac disease or vice versa? Or is there other explanation?

Reviewer #2: Topic: ‘Two – Dimensional and Doppler Trans-Thoracic Echocardiographic Patterns of suspected Paediatric Heart Diseases at Tibebe – Ghion Specialized Teaching Hospital and Adinas General Hospital, Bahir Dar, North West Ethiopia: – an experience from a LMIC’.

Authors: Tesfaye Taye Gelaw, Habtamu Bayih Engida, Abiot Tefra Alem, Amare Aschalew Yehuala, Senay Zerihun Mengste, Yalemwork Anteneh Yimer

Journal: PLOS ONE

Version 1

Date: Dec 1,2023

Dear Authors,

Thanks for bringing this important public health issue. It was an excellent initiative to investigate common indications for pediatric echocardiography and also reporting common findings.

Here below you find comments and suggestions that will help to refine your manuscript.

Abstract:

- Good.

- Please check the indications percentage as it adds up above 100% (133.4%).

- Please check and reconcile what you say detection rate. Detection rate is used when a test is compared with a gold standard (sensitivity in statistics). I don’t think you wanted to say that from what can be seen from the results in the manuscript. Here your gold standard is Echo which is compared against clinical symptoms/signs indications. Here it seems you are reporting the positive predictive value (PPV) of a given sign/symptom for picking a cardiac disease in children (as it is confirmed by Echo)

- You also reported a univariate analysis output in percentages. I don’t see here any report of statistical method in terms of P value or others tests.

Introduction:

It is too long. Please try to shorten this section.

Methods:

Settings: Please mention here the details of echocardiography machines that used (brand, model, probes, image storage capacity and access methods etc) for diagnostic purpose. Mention also here the capacity of the hospitals in terms of treatment, care and follow up of these diagnosed patients.

Analysis: Univariate analysis mentioned but no report of any statistical outputs like P value.

Please include ethical approving institution with its minutes.

In operational definition it is clear that you used the 2012 WHF criteria for RHD diagnosis given the time of your study. Please stress this in the discussion section of your paper as we have new 2023 WHF RHD criteria where borderline and other names have been removed. That way you will avoid confusion as publication of your paper if accepted will be after the new 2023 WHF guideline.

Results:

Figure 1 is good but try to make it clearer in relation to the numbers and percentages.

Page 6 indications add up above 100%.

The figures and tables are good. You have too much information and try to limit what you want to send to the readers. It looks you are reporting the positive predictive value of symptoms/signs for the diagnosis of heart disease in children. You are also reporting the common echocardiographic abnormalities in children.

You have detailed descriptive of echocardiographic abnormalities.

You may do univariate analysis and report the association between symptoms/signs and heart disease in children. That will make your study more clinically relevant.

Page 10 Tables 3-1 and 3-2 may be Tables 4-1 and 4-2. Please check that.

Discussion, conclusion and recommendations:

Please check and decide how you want to present the paper (PPV vs association between symptoms/signs and heart disease). You may revise this section and the title after that.

References: Ok

Additional comment: Please check syntax, capitalization and other minor errors in your manuscript for easy readability. Your paper can be revised after you decide what it needs to send to the readers.

**********

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Reviewer #1: Yes: Atnafu Mekonnen Tekleab

Reviewer #2: No

**********

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PLoS One. 2024 Mar 11;19(3):e0292694. doi: 10.1371/journal.pone.0292694.r002

Author response to Decision Letter 0

3 Jan 2024

Response to academic editor’s and reviewers’ comments

1. Responses to academic editor’s comment/Journal requirements:

1.1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming.

Thanks for the recommendations provided to abide with the PLOS ONE’s style requirements. The manuscript is revised and edited in such a way that suits with the requirements.

1.2. We noticed you have some minor occurrence of overlapping text with the following previous publication(s).

Yes it overlaps with the publications mentioned (probably, it might be because of repetitive referencing of the studies in our day to day clinical practice). Thanks for the in depth evaluation of our manuscript. We have re-iterated both of them in our own ways.

1.3. We note that you have stated that you will provide repository information for your data at acceptance.

Our statements regarding data availability are “Yes - all data are fully available without restriction” and “All relevant data are within the manuscript and its Supporting Information files.” We didn’t say “ I will provide repository information at acceptance”. Hence, with due respect, I ask you to see and amend it ASAP.

1.4. We are unable to open your Supporting Information file [Echo Submitted to PLOS ONE.rar].

I will Re-upload the supporting Information file. It contains all the back ground data.

Remark: Diagnosis and classification, and operational definition part are revised. They were in table format and changed to plain write up.

2. Response to reviewers comments:

Dear reviewers,

Thanks for the bold comments, complements and feedbacks you provided us. Here below are the responses for each points raised.

2.1. Review Comments to the Author and the responses

2.1.1. Reviewer 1:

2.1.1.1. Aim of the study: comments well accepted and edited. “Our aim is to describe the trans-thoracic echocardiography pattern of paediatric heart diseases and reasons of referral for echocardiography in children referred to Bahir Dar University Tibebe – Ghion Hospital and Adinas General Hospital.”

2.1.1.2. Title length: comment well accepted. The aim is well explained. “pattern”. The data were collected from two different hospitals with different levels and merging them might assume the two hospitals with same status.

2.1.1.3. Punctuation and grammar errors: Well accepted and edited ASAP.

2.1.1.4. Abstract section: comments well accepted and edited. Both the result and conclusion parts are re-iterated. In addition, key words are included. (see track changes and final manuscript version)

2.1.1.5. Introduction section: I agree with removal of paragraph – 4 on page three. It has nothing to do here at this part. ( references will nourish the methods part). Regarding paragraph – 2 on page – 4, in addition to describing the patterns, we aimed to describe the reasons that led children visit echocardiography evaluation. Hence, we would be very happy if it stays there as it is with minor rearrangement and modification. (see the revised manuscript)

2.1.1.6. End of introduction: we revised the objective statement and is now perfectly matching with your recommendation.

2.1.1.7. Methods: data collection methods and sources are included in the manuscript. In addition, who collected data and the decision on doubtful findings is also elaborated ASAP. Echo was done by pediatric cardiologist and in doubtful conditions, the adult cardiologists and radiologists will have a look at and suggest their recommendation. Any archived data with incomplete documentation was not included in the analysis. (see figure 1) Post intervention clients are included in the study as we are evaluating the echocardiography pattern of children with suspected heart disease. It reflects the magnitude of the intervention gap.

2.1.1.8. Results: comment accepted.

• For clarity, 3672 are all clients who underwent echocardiography evaluation at the two hospitals echocardiography laboratory over the four years period. The hospitals are located in an area where only 2 pediatric cardiologists are providing service. One in Gondar, North west Ethiopia and the other in Bahir Dar, where most of the Pediatric clients with suspected heart diseases are referred to for echocardiography evaluation.

• Regarding the number of tables: Yes I agree with the reduction of number of tables. Table 2 and 3 are removed. It is revised in both the Manuscript and revised manuscript with track change.

• Table 1 Heading is revised in a way it was intended to …….. and converted to fig as it is larger in size to accommodate and insert it as table. The Table is intended to show the proportion of reasons of referral for echocardiography evaluation that end up with cardiac disorders/normal findings.

2.1.1.9. Discussion: comments accepted and revised considering the inputs, comments and complements of the other reviewer too.

2.1.1.10. Thanks for all the valuable comments and complements.

2.1.2. Reviewer 2:

2.1.2.1. Abstract:

2.1.2.1.1. The “indications” is replaced by “ reasons of referral for echocardiography”. The numbers might add up to more than the total number of clients. This is because, children might be referred for echocardiography with more than one reason. We put the clarification at the bottom of the table as remark.

2.1.2.1.2. Regarding “detection rate”, comments are well accepted. It was intended to show the proportion of reasons of referrals with positive cardiac findings. It is amended and revised that way.

2.1.2.1.3. Regarding “Univariate analysis”, once again comments are well taken. It is a descriptive analysis and amended ASAP.

2.1.2.2. Introduction:

2.1.2.2.1. Too long introduction: comment is well accepted and shortened as recommended.

2.1.2.3. Methods:

2.1.2.3.1. Settings: comment accepted. The echocardiography models used for diagnostic assessment are described and mentioned. The capacity of the hospitals is elaborated with the extent of service and where the clients are getting services.

2.1.2.3.2. Analysis: comment accepted and it is descriptive analysis. Univariate analysis is used synonymously with descriptive analysis in some references and we found it that it is confusing. For clarity purpose and comforting the readers, we preferred to use the phrase “ descriptive analysis”.

2.1.2.3.3. “Ethical approval”: it is mentioned in the study design sub section. and the minute is already uploaded as a separate file during submission. In addition, as per your recommendation, I have added “Institutional Ethics Committee issued approval protocol number: 795/2023. This hospital-based retrospective observational study was approved by the Institutional Review Board of Bahir Dar University College of Medicine and Health sciences and was approved without comments.” In the disclosure part.

2.1.2.3.4. Regarding “ WHF 2012 Borderline RHD Criteria Vs. Stage A RHD”: thanks for the update. I included it in the operational definition and discussed it in the discussion part. Tried to show the difference and similarity.

2.1.2.4. Results:

2.1.2.4.1. Figure 1: comment accepted and edited. it is edited and brought with a better one. In some of our tables and figures, the percent and numbers add up more than hundred percent and the total number of cases because a single client might have more than one cardiac lesion. For example Congenital Heart disease and acquired heart disease. So the readers are not expected to add up the numbers.

2.1.2.4.2. “Indications” is revised as “reasons of referral for echocardiography”. They can be single or multiple for a single client which in turn will increase both the precent and number more than 100% and total number of cases. Hence, we recommend the readers not to add up them rather to see the proportion of reasons for referral as it appears. Remarks are there at the bottom of the tables and figures.

2.1.2.4.3. Regarding “positive predictive value” : Our intention is not to show the “positive predictive value” rather the proportion of reasons of referral for echocardiography and the cardiac findings and to show which reasons are more common and linked with more cardiac abnormalities. Re-iterated.

2.1.2.4.4. Table 3 – 1 and Table 3 – 2 are revised and you are right they were Tables 4 – 1 and 4 – 2.

2.1.2.4.5. Regarding the recommendations for use of univariate analysis and reporting associations: it is not our intention and descriptive analysis will not show association rather it is just a description.

2.1.2.4.6. Discussion, conclusion and recommendations: they all are re-visited and revised as per all the comments and complements given.

2.1.2.4.7. once again, thanks for the comments and complements.

Attachment

Submitted filename: Response to reviewers.docx

pone.0292694.s004.docx (19.9KB, docx)

Decision Letter 1

Endale Tefera

29 Jan 2024

PONE-D-23-28984R1Two – Dimensional and Doppler Trans-Thoracic Echocardiographic Patterns of suspected Pediatric Heart Diseases at Tibebe – Ghion Specialized Teaching Hospital and Adinas General Hospital, Bahir Dar, North West Ethiopia: – an experience from a LMIC.

PLOS ONE

Dear Dr. Gelaw,

Thank you for submitting your revised 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. In addition to comments from the reviewers, I have also added the below comments for major revision to your manuscript: 

Additional comments:

  1. Please add “cross-sectional study” in your study design. The terms mentioned represent the type of study (descriptive) and timeline of data collection (retrospective), not necessarily the study design.

  2. The data was collected retrospectively, understandably, from the medical records. Why was verbal consent taken from the patients and how did the authors manage this? I would have expected them to mention they got waiver of consent from IRB.

  3. The operational definition section, I know this was motivated by the reviewers’ comments on diagnosis of myocarditis. This diagnosis can be defined in the introduction or methods or discussion sections. Otherwise, it’s needless to give operational definition for all congenital or acquired diseases. It’s sufficient if they are contextually discussed where needed.

  4. The statistical section is vague. It needs clarification on what analysis was used for what (e.g., numerical variables were presented as mean±SD or median (interquartile range) based on …, categorical variables were presented …, etc.)

  5. Page 7, last paragraph, “Out of the 3, 647 pediatric clients with complete documentation and first-time visits; 2,273 children had one or more cardiac diseases on echocardiography”. Is it to mean one or more cardiac lesions? Cardiac disease is not the same as cardiac lesion.

  6. Traditionally, table 1 is meant to describe baseline characteristics of study participants, not results. In addition, the classification as neonate, infant, etc. is not appropriate as the newborn is also included in the infant category. For clarity, it’s better to mention the age classification that the authors used (e.g., 0-28 days, 1-12 months, etc). in addition, this table contains a lot of cells with zero values which made the table so redundant. Some small numbers can be lumped together as “others”. This table needs to be contracted to no more than half a page; otherwise, it will be difficult for the readership to capture the message or even to read.

  7. Figure 4 is redundant. The information has already been included in table 1.

  8. Figure 5. The figure legends are given twice, once on the left side of the figure then at the bottom. In my opinion, this figure also doesn’t add much to the message. This figure also indicates that 15 neonates (0.004*3647) were diagnosed for acquired heart diseases. My question would be what were these acquired lesions in the newborns? What was the degree of certainty?

  9. Discussion: I disagree with the last statement of the first paragraph. The authors need to emphasize their results in the context of the objective of the study. Judging the ability and skill of the referring physician was not the objective of the study. There are multitudes of reasons that physicians may refer patients, especially in setting where there are no guidelines. As a matter of fact, the authors mention that the most common reason for referral was detection of murmur, but we don’t in how many of these patients the murmur was substantiated or refuted by the cardiologists.

  10.  Page 12, last paragraph, statement about a US study doesn’t fit the context of your study and I recommend that you remove the statement and the reference.

  11. Page 13, 1st paragraph, mortality should be included as one of the reasons. Newborns with critical CHD may be misdiagnosed or may not even make it to the hospital which complicates your comparison. However, there is also an issue comparing it with a Cameroonian study and cite these reasons as explanations because the facility and infrastructure in Cameroon is not expected to be much different than that of yours. I recommend that you cite literature in a context that supports your arguments.

  12. Page 13, last but not one paragraph, again the cited literatures are from low-income similar settings but when giving explanations, the authors say the difference is because of the setting, facilities, or maternal infections. This doesn’t make sense as compared settings are not that different.

  13. The discussion section needs overhaul. My recommendation and personal preference:
    • Highlight main study findings in the 1st paragraph,
    • Give brief contextual possible explanations for the findings,
    • Similarities and differences of methodology and findings with other similar studies, rather than citing publications randomly in the 3rd paragraph,
    • Study limitations and constraints in the 4th paragraph
    • The way forward and recommendation for future work in the last paragraph
    • Only relevant literature needs to be cited. These need to be selected based on critical appraisal of their methods and findings (that way the authors can limit the list of references).

  14. Journals need to be written using their standard abbreviations and this needs to be applied throughout the reference list.

  15. PLOS ONE does not copy edit manuscripts. Therefore, the authors need to attend to grammatical, syntax and punctuation errors: preferably seek help from native English speakers if possible.

Please submit your revised manuscript by Mar 14 2024 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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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: (No Response)

**********

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: Partly

**********

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

Reviewer #1: Yes

Reviewer #2: No

**********

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

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: The authors have addressed my comments very well. The language edits, the change in the format of the table and the complete revison that they have done in the discussion section have improved the manuscript significantly.

Reviewer #2: Dear Authors,

Thanks for revising your manuscript and addressing most of the comments.

Here below you find additional comments that were partly addressed or not addressed at all to make your article more readable.

- Please stress that your paper is only descriptive and mention that no further analytic analysis was made. This will make it clear for the end users as to the questions they might have while reading your paper. Please include this as the limitation of your study and if possible quote also the reasons for that like data availability issue etc.

- Please include the interquartile range for the median age of study participants on page 7.

- Please discuss the issue of making a diagnosis of myocarditis or cardiomyopathy in the face of an underlying heart disease or mention it as a limitation as you have a group patients who ended up with it.

- You still have many figures, can it be reduced? Like what is the main difference between Stable 1 and Figure 5. They have related information. Please drop one of them

- Figure 3 is challenging for end users i.e. proportions vs clinical symptoms. However, as the authors opted out for only descriptive report, then it can be kept as it is. Please move it to supplemental section.

- Please make the recommendation short and precise and based on your study findings. It is long as it is now.

- Please address the missing capitalization and syntax issues in the paper one more time.

**********

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Reviewer #1: Yes: Atnafu Mekonnen Tekleab

Reviewer #2: No

**********

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PLoS One. 2024 Mar 11;19(3):e0292694. doi: 10.1371/journal.pone.0292694.r004

Author response to Decision Letter 1

9 Feb 2024

1. Response to Academic Editor: Thank you for the critical and valuable feedbacks and comments that nourish our work significantly.

1.1. Please add “cross-sectional study” in your study design. The terms mentioned represent the type of study (descriptive) and timeline of data collection (retrospective), not necessarily the study design.

1.1.1. Response: comment well accepted and added to the methods part.

1.2. The data was collected retrospectively, understandably, from the medical records. Why was verbal consent taken from the patients and how did the authors manage this? I would have expected them to mention they got waiver of consent from IRB.

1.2.1. Response: comment well accepted and revised (see previous review comment)

1.3. The operational definition section, I know this was motivated by the reviewers’ comments on diagnosis of myocarditis. This diagnosis can be defined in the introduction or methods or discussion sections. Otherwise, it’s needless to give operational definition for all congenital or acquired diseases. It’s sufficient if they are contextually discussed where needed.

1.3.1. Response: Comment accepted and removed and inserted ASAP.

1.4. The statistical section is vague. It needs clarification on what analysis was used for what (e.g., numerical variables were presented as mean±SD or median (interquartile range) based on …, categorical variables were presented …, etc.)

1.4.1. Response: comment well accepted and re-visited.

1.5. Page 7, last paragraph, “Out of the 3, 647 pediatric clients with complete documentation and first-time visits; 2,273 children had one or more cardiac diseases on echocardiography”. Is it to mean one or more cardiac lesions? Cardiac disease is not the same as cardiac lesion.

1.5.1. Response: It is to mean cardiac lesion. Revised as per the recommendation.

1.6. Traditionally, table 1 is meant to describe baseline characteristics of study participants, not results. In addition, the classification as neonate, infant, etc. is not appropriate as the newborn is also included in the infant category. For clarity, it’s better to mention the age classification that the authors used (e.g., 0-28 days, 1-12 months, etc). in addition, this table contains a lot of cells with zero values which made the table so redundant. Some small numbers can be lumped together as “others”. This table needs to be contracted to no more than half a page; otherwise, it will be difficult for the readership to capture the message or even to read.

1.6.1. Response 1: the baseline characteristics of study participants in our study are age and gender of children assessed. The reason we omit this one is that they are reflected in the narration, table and figures parts in one or another way.

1.6.2. Response 2: the comment on the classification of age of children assessed is well accepted and corrected as per the recommendation provided.

1.6.3. Response 3: comment regarding the size of the table is well accepted and contracted as much as possible.

1.7. Figure 4 is redundant. The information has already been included in table 1.

1.7.1. Response: comment accepted and the figure is removed.

1.8. Figure 5. The figure legends are given twice, once on the left side of the figure then at the bottom. In my opinion, this figure also doesn’t add much to the message. This figure also indicates that 15 neonates (0.004*3647) were diagnosed for acquired heart diseases. My question would be what were these acquired lesions in the newborns? What was the degree of certainty?

1.8.1. Response 1: The figure legends are duplicated. We removed the legend at the bottom.

1.8.2. Response 2: The figure’s added value in nourishing our work: It’s added value is not significant as the content in it is already there in table 1. We agree to remove it from the manuscript.

1.8.3. Response 3: The number of neonates with acquired heart disease diagnosis: They are only 2 (0.004 *501 = 2). It is from total neonates screened not from total children screened. The acquired heart lesions were Cardiomyopathy associated with perinatal asphyxia and myocarditis. We used operational definition for diagnosis of Cardiomyopathy and myocarditis.

1.9. Discussion: I disagree with the last statement of the first paragraph. The authors need to emphasize their results in the context of the objective of the study. Judging the ability and skill of the referring physician was not the objective of the study. There are multitudes of reasons that physicians may refer patients, especially in setting where there are no guidelines. As a matter of fact, the authors mention that the most common reason for referral was detection of murmur, but we don’t in how many of these patients the murmur was substantiated or refuted by the cardiologists.

1.9.1. Response 1: comment well accepted and we believe that it has extended out of the objective and it cannot provide a clue for such a judgment to be concluded. It is revised.

1.9.2. Response 2: the most common reason of referral: it only provides the documented reason of referral for echocardiography given by any health care provider. As it is a retrospective analysis of documentation at echo lab., it was not possible to get a documentation that substantiated or refuted the finding based on further clinical evaluation by cardiologists and our objective was not to substantiate or refute it. We revised this part of the discussion in such a way to be clear for readers.

1.10. Page 12, last paragraph, statement about a US study doesn’t fit the context of your study and I recommend that you remove the statement and the reference.

1.10.1. Response: comment well accepted and it is removed.

1.11. Page 13, 1st paragraph, mortality should be included as one of the reasons. Newborns with critical CHD may be misdiagnosed or may not even make it to the hospital which complicates your comparison. However, there is also an issue comparing it with a Cameroonian study and cite these reasons as explanations because the facility and infrastructure in Cameroon is not expected to be much different than that of yours. I recommend that you cite literature in a context that supports your arguments.

1.11.1. Response: comment well accepted. Reasons for higher proportion of children in the age group from one month to twelve months are updated as recommended. Evidences that doesn’t support our argument are removed.

1.12. Page 13, last but not one paragraph, again the cited literatures are from low-income similar settings but when giving explanations, the authors say the difference is because of the setting, facilities, or maternal infections. This doesn’t make sense as compared settings are not that different.

1.12.1. Response: evidences that are not substantiating our discussion are removed.

1.13. The discussion section needs overhaul. My recommendation and personal preference:

1.13.1. Response: comment well accepted and revised as much as possible to suit the recommendations provided.

1.14. Journals need to be written using their standard abbreviations and this needs to be applied throughout the reference list.

1.14.1. Response: comment accepted and done ASAP.

1.15. PLOS ONE does not copy edit manuscripts. Therefore, the authors need to attend to grammatical, syntax and punctuation errors: preferably seek help from native English speakers if possible.

1.15.1. Response : comment accepted.

2. Response to reviewer 2: thank you very much for tirelessly evaluating our work tirelessly and commenting constructively.

2.1. Please stress that your paper is only descriptive and mention that no further analytic analysis was made. This will make it clear for the end users as to the questions they might have while reading your paper. Please include this as the limitation of your study and if possible quote also the reasons for that like data availability issue etc.

2.1.1. Response: comment accepted well and revised as per the recommendation.

2.2. Please include the interquartile range for the median age of study participants on page 7.

2.2.1. Response: comment accepted and IQR is included.

2.3. Please discuss the issue of making a diagnosis of myocarditis or cardiomyopathy in the face of an underlying heart disease or mention it as a limitation as you have a group patients who ended up with it.

2.3.1. Response: comment accepted and revised.

2.4. You still have many figures, can it be reduced? Like what is the main difference between Stable 1 and Figure 5. They have related information. Please drop one of them.

2.4.1. Response: comment accepted. Stable 1, figure 4 and figure 5 are removed as they can be reflected in the other tables and figures.

2.5. Figure 3 is challenging for end users i.e. proportions vs clinical symptoms. However, as the authors opted out for only descriptive report, then it can be kept as it is. Please move it to supplemental section.

2.5.1. Response: the intention of presenting figure three here is to show the proportion of children identified with heart disease against the presenting complaints/reasons of referral for echocardiography. It is only for descriptive report. We pushed it to supplemental section.

2.6. Please make the recommendation short and precise and based on your study findings. It is long as it is now.

2.6.1. Response: comment well accepted and revised.

2.7. Please address the missing capitalization and syntax issues in the paper one more time.

2.7.1. Response: comment accepted and revised.

Reviewer 1 had no comments or feedbacks in this session.

Attachment

Submitted filename: Response to reviewers 2.docx

pone.0292694.s005.docx (19KB, docx)

Decision Letter 2

Endale Tefera

23 Feb 2024

Two – Dimensional and Doppler Trans-Thoracic Echocardiographic Patterns of suspected Pediatric Heart Diseases at Tibebe – Ghion Specialized Teaching Hospital and Adinas General Hospital, Bahir Dar, North West Ethiopia: – an experience from a LMIC.

PONE-D-23-28984R2

Dear Dr. Gelaw

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

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Kind regards,

Endale Tefera

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: Dear Authors

Thanks for addressing the concerns. Please do one more time language edits. Otherwise comments are well addressed.

**********

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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: Yes: Henok Tadele

**********

Acceptance letter

Endale Tefera

29 Feb 2024

PONE-D-23-28984R2

PLOS ONE

Dear Dr. Gelaw,

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on behalf of

Dr. Endale Tefera

Academic Editor

PLOS ONE

Associated Data

    This section collects any data citations, data availability statements, or supplementary materials included in this article.

    Supplementary Materials

    S1 Table. Proportion of children with 1.

    (DOCX)

    pone.0292694.s001.docx (17.7KB, docx)
    S1 File

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    pone.0292694.s002.zip (6.5MB, zip)
    S2 File

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    pone.0292694.s003.zip (8.7MB, zip)
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    Submitted filename: Response to reviewers.docx

    pone.0292694.s004.docx (19.9KB, docx)
    Attachment

    Submitted filename: Response to reviewers 2.docx

    pone.0292694.s005.docx (19KB, docx)

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