Real-Life Measurement of Vasoregulation in Patients with Cyanotic Congenital Heart Disease: A Feasibility Study
Round 1
Reviewer 1 Report
Comments and Suggestions for AuthorsThe article presents real-life case studies involving continuous, noninvasive blood pressure measurement in pediatric patients affected by cyanotic congenital heart disease using the SOMNOtouch NIBP cuffless device. The authors document fluctuations—mainly in diastolic blood pressure—in infants and adolescents, connecting these data to oxygen saturation and heart rate variability. The work highlights the clinical value of such monitoring for both understanding pathophysiological mechanisms and evaluating pharmacological interventions in this vulnerable population. Overall, the work is innovative and original in the pediatric context but needs improved presentation, methodological rigor, and sample expansion to achieve robust scientific impact
Here are my concerns:
- The study design is limited to only three cases, without controls or rigorous statistical analysis, which restricts the external validity of the results. There is the need for prospective studies with larger patient groups and controls to objectively demonstrate the added value of cuffless monitoring in comparison to standard methods.
- Selection and interpretation bias risks are high due to the limited scope.
- English language quality and manuscript structure are insufficiently refined.
- There's the need to include comparisons with other monitoring methodologies and expand on limitations
Enhance the manuscript structure and language by editing for fluency and clarity.
Author Response
Thank you very much for your valuable comment. We expressly agree that our work is purely observational in nature. The phenomenon described was observed in three patients, which is why we present these three cases in detail in the publication.
In order to emphasize this observational nature more clearly and avoid misunderstandings, we have adjusted the title and conclusion accordingly. We would also like to point out that our work does not claim to be generalizable but is intended as an initial descriptive contribution to a clinical finding that has been little described to date.
Please find below a point-to-point answer to your concerns:
- The study design is limited to only three cases, without controls or rigorous statistical analysis, which restricts the external validity of the results. There is the need for prospective studies with larger patient groups and controls to objectively demonstrate the added value of cuffless monitoring in comparison to standard methods.
We have amended the statement in the article to refer to observational findings. We agree that further prospective studies are required. The added value of the cuffless method is that short-term BP changes cannot be detected using standard methods (e.g. cuff) due to their discontinuous nature. We have now included both in the discussion.
- Selection and interpretation bias risks are high due to the limited scope.
See above, we are now writing about observational data. Especially the Conclusions section was adapted.
- English language quality and manuscript structure are insufficiently refined.
You were also absolutely right that the English in our article was inadequate in some places. We have reviewed the text again and revised it to improve the English.
- There's the need to include comparisons with other monitoring methodologies and expand on limitations
We have included some sentences about this in the discussion and 3 new references (10-13).
Reviewer 2 Report
Comments and Suggestions for Authors
This is a promising pilot study that introduces a novel, non-invasive method for monitoring real-time vasoregulation in a critically ill and difficult-to-study population: infants and children with complex congenital heart disease (CHD). The potential for this technology to provide insights into pathophysiology and pharmacotherapy is significant. The case studies are illustrative and the connection to hypoxic pathways is well-argued. Please also address the following comments before consideration for publication.
- Could the authors offer more details about the blood pressure evaluation? Including the detailed assessment process and raw data, evaluation accuracy, etc.
- The formatting and Typos should be carefully checked. For example, “pulse walve velocity” in Line 190 and Line 235, should be “pulse wave velocity”.
- Restructure the manuscript: The Methods section should describe the device, calibration, and patients (demographics, diagnoses) concisely. All findings (the plots, correlations, trends) should be moved to a unified Results section. The Discussion should then be reserved for interpreting these findings in the context of the wider literature, without introducing new results.
Author Response
Thank you very much for your helpful comments.
Please find below a point-to-point answer to your concerns:
1. Could the authors offer more details about the blood pressure evaluation? Including the detailed assessment process and raw data, evaluation accuracy, etc.
We included the name of the blood pressure device (Welsh Allyn). I confirm the uncertainty of the conventional cuff measurements in infants due to motion artifacts. It is the advantage of the cuffless method to measure the blood pressure trends free from motion artifacts at night. The absolute blood pressure values - that depends from the cuff method - is not so important if we try to understand vasoregulation.
Furthermore, we have added a new paragraph to the methods section, which describes data handling in more detail.
2. The formatting and Typos should be carefully checked. For example, “pulse walve velocity” in Line 190 and Line 235, should be “pulse wave velocity”.
The spelling has been checked and the English adapted.
3. Restructure the manuscript: The Methods section should describe the device, calibration, and patients (demographics, diagnoses) concisely. All findings (the plots, correlations, trends) should be moved to a unified Results section. The Discussion should then be reserved for interpreting these findings in the context of the wider literature, without introducing new results.
I tried to improve the structure of the text.
Reviewer 3 Report
Comments and Suggestions for AuthorsGeneral Assessment
The manuscript reports on real-life monitoring of vasoregulation in three pediatric patients with cyanotic congenital heart disease using a cuffless blood pressure device (SOMNOtouch™-NIBP). The topic is relevant, particularly for non-invasive monitoring in vulnerable clinical populations. However, the manuscript presents a descriptive case series rather than a structured study, and several essential scientific and ethical issues must be addressed before it can be considered for publication.
-Ethical Issues
The ethical statement is incomplete and insufficient for a study involving infants and children. The manuscript states that ethical approval was waived because Holter ECG monitoring is part of clinical routine, but this waiver cannot be self-granted by the authors. Any research involving minors requires either formal ethics approval or a documented ethics committee waiver.
Specific issues:
Issue Concern
Use of infants and minors Requires IRB oversight and parental consent
No registry or protocol number Missing ethics documentation
Device manufacturer involvement One author is an employee; conflict of interest must be clearly disclosed
Calibration method involves clinical measurements Not automatically exempt from ethics review
Recommendation: Provide IRB approval number or official waiver, and clarify consent procedures.
-Methodological Issues
Study Design
The work is a case series (n=3) but is presented as a study with generalizable conclusions.
There are no inclusion criteria, exclusion criteria, or predefined outcomes.
The observational nature is not clearly acknowledged.
Device Calibration and Measurement
A single manual cuff measurement is used to calibrate the entire blood pressure record. This method is known to produce progressive drift in pulse transit time devices.
No validation against gold-standard reference methods is provided.
Motion artifacts and calibration limitations are acknowledged but not technically addressed.
Data Analysis
Correlation values are reported without statistical significance (p-values) or confidence intervals.
No repeated-measures or time-series analysis was performed.
Pharmacological therapy, oxygenation, age, and postoperative status are major uncontrolled confounders.
Recommendation: Reclassify as a descriptive case series with exploratory correlations rather than causal findings.
-Clarity and Structure of Writing
Strengths:
Clinical cases are well described
Figures are clear
Weaknesses:
English grammar and phrasing require professional revision
The discussion overextends conclusions beyond the presented data
Several sections repeat background concepts rather than interpreting the case results
The manuscript uses absolute language such as “proof,” which is not supported by the limited data
Recommendation: Replace causal claims with more cautious language such as “suggest,” “indicate,” or “are consistent with.”
-Required Major Revisions
Area Required Action
Ethics Provide IRB approval or waiver number
Study classification Identify clearly as a case series
Statistics Include p-values and confidence intervals
Language Professional English editing recommended
Conflict of interest Expand and clarify manufacturer involvement
Claims Avoid overstating conclusions
Suggested Rewording of Key Claim
Current:
"We demonstrate the first measurements to monitor vasoregulation under real life conditions..."
Suggested:
"We present preliminary observational data suggesting that non-invasive pulse-transit-time monitoring may help explore vasoregulatory responses in cyanotic congenital heart disease."
Decision: Major Revision Required
The manuscript addresses a relevant topic but does not yet meet ethical, methodological, or reporting standards expected for a scientific publication. With restructuring as a case series, improved ethical documentation, and revision of claims, the work may be suitable for reconsideration.
Author Response
The ethical statement is incomplete and insufficient for a study involving infants and children. The manuscript states that ethical approval was waived because Holter ECG monitoring is part of clinical routine, but this waiver cannot be self-granted by the authors. Any research involving minors requires either formal ethics approval or a documented ethics committee waiver.
In 2021, I submitted an inquiry to the ethics committee of the University Würzburg asking whether an application was necessary for retrospective analysis of Holter ECG’s (Number 20210505 04). I have received a written response stating that an ethics application is not necessary.
Device manufacturer involvement One author is an employee; conflict of interest must be clearly disclosed. The employee help me to read the data from the device. It is my idea to use the device in infants and to publish the interesting data. The exact contributions can be found under Author contributions.
Study Design: The work is a case series (n=3) but is presented as a study with generalizable conclusions.
There are no inclusion criteria, exclusion criteria, or predefined outcomes.
The observational nature is not clearly acknowledged.
We expressly agree that our work is purely observational in nature. The phenomenon described was observed in three patients, which is why we present these three cases in detail in the publication.
In order to emphasize this observational nature more clearly and avoid misunderstandings, we have adjusted the title and conclusion accordingly. We would also like to point out that our work does not claim to be generalizable but is intended as an initial descriptive contribution to a clinical finding that has been little described to date.
Data Analysis: Correlation values are reported without statistical significance (p-values) or confidence intervals.No repeated-measures or time-series analysis was performed. Pharmacological therapy, oxygenation, age, and postoperative status are major uncontrolled confounders.
I agree, we avoided to indicate statistics from many time series from two patients. Some are highly significant, other not. The paper should show the feasibility to measure blood pressure fluctuations non-invasively. I work in a private praxis. I hope that clinicians will read the paper and use the device for prospective measurements.
Round 2
Reviewer 3 Report
Comments and Suggestions for AuthorsAll points were adequately addressed.
Author Response
We further include the sentence in line 2018:
However, pharmacological therapy, age, and postoperative status are major uncontrolled confounders in this observational study and we avoided to indicate statistics from many time series from only three patients.
These are the answers in the first revision
The ethical statement is incomplete and insufficient for a study involving infants and children. The manuscript states that ethical approval was waived because Holter ECG monitoring is part of clinical routine, but this waiver cannot be self-granted by the authors. Any research involving minors requires either formal ethics approval or a documented ethics committee waiver.
In 2021, I submitted an inquiry to the ethics committee of the University Würzburg asking whether an application was necessary for retrospective analysis of Holter ECG’s (Number 20210505 04). I have received a written response stating that an ethics application is not necessary.
Device manufacturer involvement One author is an employee; conflict of interest must be clearly disclosed. The employee help me to read the data from the device. It is my idea to use the device in infants and to publish the interesting data. The exact contributions can be found under Author contributions.
Study Design: The work is a case series (n=3) but is presented as a study with generalizable conclusions.
There are no inclusion criteria, exclusion criteria, or predefined outcomes.
The observational nature is not clearly acknowledged.
We expressly agree that our work is purely observational in nature. The phenomenon described was observed in three patients, which is why we present these three cases in detail in the publication.
In order to emphasize this observational nature more clearly and avoid misunderstandings, we have adjusted the title and conclusion accordingly. We would also like to point out that our work does not claim to be generalizable but is intended as an initial descriptive contribution to a clinical finding that has been little described to date.
Data Analysis: Correlation values are reported without statistical significance (p-values) or confidence intervals.No repeated-measures or time-series analysis was performed. Pharmacological therapy, oxygenation, age, and postoperative status are major uncontrolled confounders.
I agree, we avoided to indicate statistics from many time series from two patients. Some are highly significant, other not. The paper should show the feasibility to measure blood pressure fluctuations non-invasively. I work in a private praxis. I hope that clinicians will read the paper and use the device for prospective measurements.
