Practical Application of a New Cuffless Blood Pressure Measurement Method

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

Overall, the manuscript presents a study on the evaluation of cuffless blood pressure measurement using the CardioQVARK device in different patient groups. The authors aimed to determine the reliability of this technology for assessing blood pressure in clinical settings. Below is a review of the manuscript:

1. Introduction: The introduction provides a clear and concise overview of the importance of cuffless blood pressure measurement and the need for a method that can be used anytime and anywhere. However, it would be helpful to include a brief background on existing cuffless blood pressure measurement methods and their limitations to provide context for the study.

2. Methods: The study design and the methodology are adequately described. The sample size and patient demographics are provided, which adds credibility to the results. However, additional details are needed regarding the recruitment process and how patients were allocated into different groups (normal blood pressure, high blood pressure, compensated high blood pressure).

3. Statistical Analysis: The authors mention that the statistical analysis plan was based on the IEEE Standard for Wearable Cuffless Blood Pressure Devices. While this is appropriate, it would be beneficial to include a summary of the key statistical tests used to compare the measurements between the CardioQVARK device and the cuff-based sphygmomanometer.

4. Results: The results are presented in a clear and concise manner. The comparison of systolic and diastolic blood pressure measurements between the CardioQVARK device and the cuff-based sphygmomanometer is well-documented. The Bland-Altman plots used to estimate the precision of cuffless measurements are appropriate for this type of study.

5. Discussion: The discussion provides a comprehensive analysis of the results. The finding that the CardioQVARK device generally shows an error of 3-4 mm Hg in systolic and diastolic blood pressure measurements is an important observation. The breakdown of errors in different patient groups (prehypertension, normotensive, stage 1, and stage 2) adds valuable insight to the study.

6. Conclusion: The conclusion is well-supported by the study results. The statement that the cuffless blood pressure technology developed and tested in this study has shown great precision in different patient groups is a strong claim. However, it would be beneficial to discuss potential limitations and areas for future research to provide a balanced perspective.

7. Language and Clarity: The manuscript is well-written with clear and concise language, making it easy to follow. However, there are a few minor grammatical errors that need to be addressed.

8. Figures and Tables: The inclusion of Bland-Altman plots would be an excellent addition to the manuscript, as it would visually demonstrate the agreement between the two methods of blood pressure measurement.

In summary, the manuscript presents valuable findings on the evaluation of cuffless blood pressure measurement using the CardioQVARK device. With some minor improvements and additional visualizations, this study has the potential to contribute significantly to the field of blood pressure monitoring. Consider addressing the mentioned points for a more comprehensive and robust manuscript.

Comments on the Quality of English Language

Overall, the quality of the English language in the manuscript is good. The text is generally clear and understandable. However, there are a few areas where improvements can be made:

1. Sentence Structure: Some sentences are quite long and complex, which may make it challenging for readers to follow. Consider breaking longer sentences into smaller ones to improve readability.

2. Inconsistent Capitalization: There are instances where certain words are capitalized unnecessarily (e.g., "CardioQVARK Device," "SBP," "DBP"). Ensure consistent capitalization throughout the manuscript.

3. Abbreviations and Acronyms: When introducing abbreviations or acronyms, it is essential to provide their full forms upon first use. For example, "PPG" is first mentioned without explanation, and it is later clarified as "Photoplethysmography." Include the full form when introducing these terms.

4. Missing References: Some statements, such as references to IEEE standards, are made without specific citations. Ensure that all claims and information are properly supported by references.

5. Clear Headings: The manuscript could benefit from more informative section headings. For example, instead of "2. Materials and Methods," consider using headings that provide more context, such as "2.1. Study Participants" and "2.2. Blood Pressure Measurement and Data Acquisition."

6. Figure and Table References: In the text, refer to figures and tables explicitly (e.g., "Figure 1," "Table 1") to help readers locate the corresponding visuals easily.

7. Consistent Tense: Be mindful of using consistent verb tenses throughout the manuscript. For example, in the Introduction, both past tense and present tense are used. Choose one and stick to it.

8. Clarity in Methods: The section "2.2. Blood Pressure Measurement and Data Acquisition" could be further clarified and organized. Provide more details on the data collection procedure and the apparatus used.

9. Grammar and Punctuation: While the overall grammar and punctuation are satisfactory, it would be beneficial to perform thorough proofreading to catch any minor errors or inconsistencies.

Author Response

Reviewer 1 wrote that:

1. Introduction: The introduction provides a clear and concise overview of the importance of cuffless blood pressure measurement and the need for a method that can be used anytime and anywhere. However, it would be helpful to include a brief background on existing cuffless blood pressure measurement methods and their limitations to provide context for the study.

Reply №1: We have added the changes to the introduction with the appropriate links. Also in the text in the discussion section are examples of studies of cuffless blood pressure measurement with limitations that may be encountered when using. “Cuffless blood pressure measurement devices are emerging as a convenient and tolerable alternative to cuff-based devices [32.       Evaluation of the Accuracy of Cuffless Blood Pressure Measurement Devices: Challenges and Proposals. Ramakrishna Muk-kamala, Mohammad Yavarimanesh, Keerthana Natarajan, Jin-Oh Hahn, Konstantinos G. Kyriakoulis, Alberto P. Avolio and George S. Stergiou. Hypertension. 2021;78:1161–1167 https://doi.org/10.1161/HYPERTENSIONAHA.121.17747]. However, there are several limitations to cuffless blood pressure measurement devices that should be considered. For instance, the accuracy of cuffless blood pressure measurement devices is still being evaluated, and there remain challenges in ensuring the accuracy of such devices [33.   Cuffless Blood Pressure Devices. Corey K Bradley, Daichi Shimbo, David Alexander Colburn, Daniel N Pugliese, Raj Pad-wal, Samuel K Sia, and D Edmund Anstey. Am J Hypertens. 2022 May; 35(5): 380–387. doi: 10.1093/ajh/hpac017.]”.

1. Methods: The study design and the methodology are adequately described. The sample size and patient demographics are provided, which adds credibility to the results. However, additional details are needed regarding the recruitment process and how patients were allocated into different groups (normal blood pressure, high blood pressure, compensated high blood pressure).

Reply №2: When we included patients in the study, we did not divide them into separate groups. We did not select patients individually.

1. Statistical Analysis: The authors mention that the statistical analysis plan was based on the IEEE Standard for Wearable Cuffless Blood Pressure Devices. While this is appropriate, it would be beneficial to include a summary of the key statistical tests used to compare the measurements between the CardioQVARK device and the cuff-based sphygmomanometer.

Reply №3: Dear reviewer, according to the IEEE Standard for Wearable Cuffless Blood Pressure Measuring Devices, the most valuable statistics in terms of measurement quality of the new device are the description of deviations (errors) from Korotkoff method (Mean difference (MD), the mean absolute difference (MAD) and mean absolute percentage difference (MAPD) and their distribution characteristics) and the Bland-Altman plot. We list these methods in Section 2.4. Statistical Analysis. Criterial comparison was not implied according to IEEE Standard.

1. Language and Clarity: The manuscript is well-written with clear and concise language, making it easy to follow. However, there are a few minor grammatical errors that need to be addressed.

Reply №4: Our text has been edited in English by MDPI. The text was reviewed for correct use of grammar and common technical terms and edited to a level suitable for publication of the study in a scientific journal.

1. Figures and Tables: The inclusion of Bland-Altman plots would be an excellent addition to the manuscript, as it would visually demonstrate the agreement between the two methods of blood pressure measurement.

Reply №5: Dear reviewer, Bland-Altman plots are already included as Figure 2 and Figure 4.

Reply Comments on the Quality of English Language

We have considered all your valuable comments. Our text has been edited in English by MDPI (date 02/10/2023. English editing ID: English-71913).

 

 

Reviewer 2 Report

Comments and Suggestions for Authors

 

Gogiberidze and colleagues present a study evaluating the performance of the CardioQVARK device (which, I understand, they developed themselves) in cuff-less measuring systolic and diastolic blood pressure.

The issue is of clinical relevance. The study design is appropriate to answer the research question, the analysis appears to have been well conducted.

However, there are some issues, that need to be addressed.

1) The importance of this new device is overstated (Introduction), and

2) the quality of presentation is currently poor. Indeed, some results are presented in the section Methods, and the linguistic quality is insufficient. Authors may need the help of a native English speaker with experience in Medicine.

3) Authors validated the CardioQVARK device following the IEEE recommendations. However, very recently, the European Society of Hypertension has released updated recommendations [Stergiou GS et al. European Society of Hypertension recommendations for the validation of cuffless blood pressure measuring devices: European Society of Hypertension Working Group on Blood Pressure Monitoring and Cardiovascular Variability. J Hypertens. 2023. doi: 10.1097/HJH.0000000000003483.]. These should be considered (see specific comment below).

4) Furthermore, and most importantly, the conclusions are only partially correct. While this study shows that the CardioQVARK device meets the standards of IEEE, the Bland-Altman analysis indicates that the cuff-less measurement of the diastolic blood pressure has a significant bias. Although the difference was small and likely of minimal (if at all) clinical relevance, this might have epidemiological relevance and make the investigated device not suited for screening of arterial hypertension (despite meeting the IEEE standards). This needs to be transparently acknowledged, and extensively discussed, in the revised Discussion.

 

The literature is globally well-done. However, two references point to conference abstracts (from 2006, Ref #18, and 2013, #13). Meanwhile, these results should have been published. Authors should cite the corresponding paper instead. If, on the opposite, after 17, respectively 10, years, these studies have still not been accepted for publication, this is potentially a sign of bad science (which has been rejected by several journals, or of a project that has still not been completed). In this latter case, Authors should cite a different work (or simply delete this reference).

 

Several specific comments are provided and must be addressed.

 

Line 23: “It is extremely important and relevant to obtain a method…” -> “It might be nice and useful to dispose about a reliable method…”

 

Line 25: “was to reliably evaluate blood pressure using the…” -> “was to evaluate blood pressure measurement through the…”

 

Line 28: what is “compensated high blood pressure”?  Current guidelines differentiate:

-       Optimal BP

-       Normal BP

-       High-normal BP

-       Hypertension (which is then graded into Grade 1, 2 and 3); isolated systolic hypertension and isolated diastolic hypertension.

[Mancia G, et al. 2023 ESH Guidelines for the management of arterial hypertension The Task Force for the management of arterial hypertension of the European Society of Hypertension Endorsed by the European Renal Association (ERA) and the International Society of Hypertension (ISH). J Hypertens. 2023 Jun 21. doi: 10.1097/HJH.0000000000003480. Epub ahead of print.]

 

Line 29: “sec” -> “s”

 

Lines 35-36: this is pretty funny. The IEEE provides standards and requirements. However, the data management plan and the statistical analysis plan must be developed for every single study. You should not have obtained it by an organization, but you are expected to have developed (and adapted and applied) it yourself.

 

Line 40: “(MAD) was for SBP” -> “(MAD) for SBP”

 

Lines 41-42 (“Based on our study we can conclude that that CardioQVARK is generally wrong by 3-4 mm Hg, both in SBP and DBP”): delete.

 

Lines 42-44: improve the English please.

 

Lines 44-46: “Judging by the IEEE recommendations, we do not have an excess of 7 mm Hg. The largest error reached 4.2 mm Hg in the high blood pressure group.  At the same time…” -> “The largest error reached 4.2 mm Hg in the high blood pressure group. We therefore never reached an error in excess of 7 mmHg, the upper boundary that would be acceptable for the IEEE recommendations. We also never reached a mean error of 5 mmHg, the upper boundary that would be acceptable according to the very recent ESH recommendations [Stergiou GS et al, J Hypertens, 2023 doi: 10.1097/HJH.0000000000003483.]. At the same…”

 

Line 46: “systolic pressure” -> “systolic blood pressure”

 

Line 48: this becomes clear while reading in full your manuscript (including the Discussion), but it is not clear while reading (just) the Abstract. While reading this, the question arises whether the CardioQVARK  is an iPhone app or a device / technology you developed? Is this an academic project or a commercially available tool? This should be clearly stated (Abstract - Introduction), so to make it clear to the readership (also to those just reading the Abstract in PubMed).

 

Lines 56-58: “Monitoring blood pressure (BP) measures is critical to reducing the risk of cardiovascular disease [7, 57 8].” -> “Monitoring blood pressure (BP) is critical to identify and adequately treat this important cardiovascular risk factor [7, 57 8].”

 

Line 61: “is cumbersome, not always accurate, and may have” -> “is cumbersome, and may deliver”

 

Lines 62-63: “non-compliance with generally accepted measurement recommendations”: delete.

 

Lines 63-64: “and many more”: delete.

 

Lines 64-65: “Thus, there is a need for simple, non-invasive wireless monitoring systems that can solve some of these problems, allow wider” -> “Thus, non-invasive wireless monitoring systems are an appealing development, helping to address some of these limitations, and allowing a wider”

 

Lines 69-72: please substitute “PTT” and “PPG” with full-wording.

 

Line 71: “One study used the…”: please cite this study at the end of this sentence.

 

Line 72: “recording ECG and” -> “recording of ECG and”

 

Lines 73-75: please correct and improve the English in these sentences (i.e., reformulate them in correct English).

 

Line 76 (“validate a method”): which one? You mention above that "there are variable models" (lines 70-71) and that the CardioQVARK device was already used in "one study" (lines 71-72). Which other device did you aim to validate?

(While reading the manuscript up to its end, it becomes clear that you assessed again the same CardioQVARK device, i.e. apparently repeating the previous study you are referring to on lines 71-72, but this time following the IEEE requests, in order to formally validate it. This should be clearly stated in the Introduction section.

 

Line 80: “It is a prospective cohort study”:

1)    -> “This is a prospective…”

2)    Why cohort study? I have the impression you just validated the device, against standard methods, in all participants (subdivided in various blood pressure categories). You did not compare two cohorts. Thus, this is rather a prospective, observational study. Not a cohort study. Modify this sentence into: “This is a prospective observational study conducted…”

 

Line 87 (“167 subjects, 64 women and 102 men between 18 and 88 were recruited”): this should belong (and must be moved) to the section Results. Here, you should state how many patients/probands you were aiming to recruit, and how this number was calculated (I guess, you decided the sample size according to the IEEE recommendations). In the Discussion section, you should add that this number was slightly lower than the sample size currently recommended (n=185) by the very recent ESH recommendations [Stergiou GS et al, J Hypertens, 2023 doi: 10.1097/HJH.0000000000003483.].

 

Line 88: “medications in force were” -> “medications were”

 

Table 1: move Table 1 to the section Results.

Table 1:

-       “criteria” -> “characteristic”

-       Lines “Age>60”, “Age>75”, “Age<40”: most importantly, provide mean and SD (if normally distributed) or median and IQR (if non-parametrically distributed). Numbers in (arbitrarily chosen) discrete categories (of this continuous variable) are optional (you might keep them if you want to, or delete them if you prefer, I don't care).

-       “LV DD of 2 and 3 grade”: reformulate in correct Engish

-       “Vessel wall stiffness”: how was vessel wall stiffness assessed? (e.g.: pulse-wave velocity, flow-mediated dilation, AASI, pulse pressure, biomarkers of endothelial function, …) This must be explained in the Methods section.

 

Line 96 (“At the first stage of the study observers training was provided”): reformulate in better English.

 

Line 98: “apparatus” -> “device”

 

Line 100: what dose “HBS” stand for? Reformulate in full words.

 

Line 104: “30 sec” -> either “30 seconds” or “30 s”

 

Lines 110-111: “the mean values of the two observers were used as reference measurements.” -> “the mean value of the two observers was used as reference.”

 

Lines 115, 124, 200, …: “PPG” -> “photoplethysmography”

 

Table 2: Nice table! However, this belongs to the section Results. Please move it there.

 

Line 137: “IEEE” -> “Institute of Electrical and Electronics Engineers”

-       There are standards, for example, from the European Society of hypertension [Stergiou GS et al. European Society of Hypertension recommendations for the validation of cuffless blood pressure measuring devices: European Society of Hypertension Working Group on Blood Pressure Monitoring and Cardiovascular Variability. J Hypertens. 2023. doi: 10.1097/HJH.0000000000003483.], which should have been considered as well. Indeed, IEEE is a technology association, while in clinical medicine (especially if you aim at proposing a screening method) it is pivotal to also include clinical considerations. Do the recommendations from IEEE align with the ones of ESH? If you look at the ESH paper, Table 4, you will notice that the current ESH recommendations are slightly stricter than the IEEE standards. Globally, it looks like that for most aspects (and at least looking at the whole group of patients) the tested device satisfies also these most stringent criteria (mean BP difference <5mmHg±8mmHg, although I did not verify whether this holds true also for all subgroups), and this should be stated (it strengthens your study). Please revise your Discussion taking these recommendations (number of subjects to include, reference method, accepted BP difference, …) into account and discuss these aspects.

è By the way, the recommendations from the ESH you are citing in Ref #25 have recently been updated (the same reference provided here above). Please double check that they still correspond with your protocol. If not, discuss and outline differences and potential limitations.

 

Lines 139-140: “measurements of cuffless method. Mean” -> “measurements. Mean”

 

Lines 153-154: “61.1% were males.” –> “61.1% were males (Table 1).”

 

Line 157: “sphygmomanometer. The mean…” -> “sphygmomanometer (Table 2). The mean…”

 

Lines 160-162: “The aim of this paper is to validate a method for non-invasive blood pressure measurement method based on the IEEE Standard for Wearable Cuffless Blood Pressure Devices. This standard has two-phase” -> “The IEEE Standard for Wearable Cuffless Blood Pressure Devices foresees a two-phase”

 

Line 168: what does “BHS” stand for?

 

Line 177: “the SBP and DBP values” -> “the SBP values”

Line 179: “based on a cuff (Figure 2, Figure 3, Figure 4, Figure 5).” -> “based on a cuff , without any trend over the range of included BP values (Table 4, Figures 2 and 3), while the DBP values were slightly but statistically significantly lower (mean bias -1.02 (95%-CI -1.65 to -0.38)) (Table 4, Figures 4 and 5).”

 

Line 182 (“The resulting raw MD composed -0.05”): what do you mean with “composed”? Please check and correct the English of this sentence.

 

Line 186 (“Density is a bit bimodal”): either it showed a bimodal distribution or not (it cannot be “a bit bimodal”). Please decide (either “density plots suggested a bimodal distribution” or “density plots suggested a roughly normal distribution”: since just one bar is lower between 2 “tall” histograms, I am personally not that sure this can be called a bimodal distribution) and reformulate accordingly

 

Lines 191-192: although such a difference is likely irrelevant from a clinical perspective, this is a systematic, significant bias of the estimation, and should be reported as such in the body of the manuscript. This is even more important if you propose this technique as a screening method (which is a wrong conclusion), because even such small differences may have epidemiological relevance (on a population scale).

 

Line 198: “provides” -> “is a valuable initiative, since it has the potential of achieving”

 

Line 201: “taken in large sample” -> “taken in a large sample”

 

Line 203: “using standards of” -> “according to the standards of”

 

Lines 205-206: “that minimized our study limitations” -> “overcoming some of the limitations of our previous study [24].”

 

Line 207:  “values definite by” -> “measurements of”

 

Line 208: “and for DBP was” -> “while for DBP it was”

 

Lines 211-216: reformulate in better, correct English.

 

Lines 217-219: This partly repeats lines 211-216. Please consider deleting these lines.

Additionally (Line 218): "the most accurate (...) BP": SBP or DBP?

 

Line 223: “It can be used” -> “It could be used”

 

Line 224: “In this case, the patient” -> “The great advantage and appeal of such a method is that the patient”

 

Line 224: “need an additional” -> “need any additional”

 

Lines 224-225: “only mobile phone” -> “only a smart phone”

 

Line 228: “corruption”: this is the wrong word. Reformulate in better English (e.g. bias, confounding, modification, …).

 

Limitations (current lines 226-228) and Conclusions (current lines 229-232):

Both in Limitations and Conclusions, you should discuss the significant bias of agreement detected for DBP. This is clinically probably not relevant, but might have epidemiological implications, especially if this method would be used for screening purposes (in research on salt-sensitive hypertension and on treatment of arterial hypertension, respectively in epidemiological studies aiming at determining BP cut-off values, such small differences have shown to potentially have a significant public health impact). Although you meet the requirements of IEEE, this result demonstrates that diastolic-only hypertension might be overseen, so that this method is not be suitable for screening. This is indeed a very important conclusion that you must transparently report and discuss.

Comments on the Quality of English Language

Please see above.

Author Response

Reviewer 2 wrote that:

1. the quality of presentation is currently poor. Indeed, some results are presented in the section Methods, and the linguistic quality is insufficient. Authors may need the help of a native English speaker with experience in Medicine.

Reply №1: Our text has been edited in English by MDPI (date 02/10/2023. English editing ID: English-71913). The text was reviewed for correct use of grammar and common technical terms and edited to a level suitable for publication of the study in a scientific journal.

2. Authors validated the CardioQVARK device following the IEEE recommendations. However, very recently, the European Society of Hypertension has released updated recommendations[Stergiou GS et al. European Society of Hypertension recommendations for the validation of cuffless blood pressure measuring devices: European Society of Hypertension Working Group on Blood Pressure Monitoring and Cardiovascular Variability. J Hypertens. 2023. doi: 10.1097/HJH.0000000000003483.]. These should be considered (see specific comment below).

Reply №2: Corrected.

3. Furthermore, and most importantly, the conclusions are only partially correct. While this study shows that the CardioQVARK device meets the standards of IEEE, the Bland-Altman analysis indicates that the cuff-less measurement of the diastolic blood pressure has a significant bias. Although the difference was small and likely of minimal (if at all) clinical relevance, this might have epidemiological relevance and make the investigated device not suited for screening of arterial hypertension (despite meeting the IEEE standards). This needs to be transparently acknowledged, and extensively discussed, in the revised Discussion.

Reply №3: Corrected.

4. The literature is globally well-done. However, two references point to conference abstracts (from 2006, Ref #18, and 2013, #13). Meanwhile, these results should have been published. Authors should cite the corresponding paper instead. If, on the opposite, after 17, respectively 10, years, these studies have still not been accepted for publication, this is potentially a sign of bad science (which has been rejected by several journals, or of a project that has still not been completed). In this latter case, Authors should cite a different work (or simply delete this reference).

Reply №4: Corrected.

5. Line 23: “It is extremely important and relevant to obtain a method…” -> “It might be nice and useful to dispose about a reliable method…”

Reply №5: Corrected.

6. Line 25: “was to reliably evaluate blood pressure using the…” -> “was to evaluate blood pressure measurement through the…”

Reply №6: Corrected.

7. Line 28: what is “compensated high blood pressure”? Current guidelines differentiate: 
   • Optimal BP
   • Normal BP
   • High-normal BP
   • Hypertension (which is then graded into Grade 1, 2 and 3); isolated systolic hypertension and isolated diastolic hypertension. [Mancia G, et al. 2023 ESH Guidelines for the management of arterial hypertension The Task Force for the management of arterial hypertension of the European Society of Hypertension Endorsed by the European Renal Association (ERA) and the International Society of Hypertension (ISH). J Hypertens. 2023 Jun 21. doi: 10.1097/HJH.0000000000003480. Epub ahead of print.]

Reply №7: “compensated high blood pressure” - Achieving the target blood pressure level during treatment in a patient with arterial hypertension of 2-3 degrees of increase.

8. Line 29: “sec” -> “s”

Reply №8: Corrected.

9. Lines 35-36: this is pretty funny. The IEEE provides standards and requirements. However, the data management plan and the statistical analysis plan must be developed for every single study. You should not have obtained it by an organization, but you are expected to have developed (and adapted and applied) it yourself.

Reply №9: We adapted and applied the IEEE standards in accordance with the characteristics of our sample and our tasks.

10. Line 40: “(MAD) was for SBP” -> “(MAD) for SBP”

 

Reply №10: Corrected.

11. Lines 41-42 (“Based on our study we can conclude that that CardioQVARK is generally wrong by 3-4 mm Hg, both in SBP and DBP”): delete.

Reply №11: Corrected.

12. Lines 42-44: improve the English please.

Reply №12: Corrected.

13. Lines 44-46: “Judging by the IEEE recommendations, we do not have an excess of 7 mm Hg. The largest error reached 4.2 mm Hg in the high blood pressure group. At the same time…” -> “The largest error reached 4.2 mm Hg in the high blood pressure group. We therefore never reached an error in excess of 7 mmHg, the upper boundary that would be acceptable for the IEEE recommendations. We also never reached a mean error of 5 mmHg, the upper boundary that would be acceptable according to the very recent ESH recommendations [Stergiou GS et al, J Hypertens, 2023 doi: 10.1097/HJH.0000000000003483.]. At the same…”

Reply №13: Corrected.

14. Line 46: “systolic pressure” -> “systolic blood pressure”

Reply №14: Corrected.

15. Line 48: this becomes clear while reading in full your manuscript (including the Discussion), but it is not clear while reading (just) the Abstract. While reading this, the question arises whether the CardioQVARK is an iPhone app or a device / technology you developed? Is this an academic project or a commercially available tool? This should be clearly stated (Abstract - Introduction), so to make it clear to the readership (also to those just reading the Abstract in PubMed).

Reply №15: We developed a method for analyzing ECG and photoplethysmography (PPG) waveforms. This method can be adapted to any device for recording ECG and pulse waves.

16. Lines 56-58: “Monitoring blood pressure (BP) measures is critical to reducing the risk of cardiovascular disease [7, 57 8].” -> “Monitoring blood pressure (BP) is critical to identify and adequately treat this important cardiovascular risk factor [7, 57 8].”

Reply №16: Corrected.

17. Line 61: “is cumbersome, not always accurate, and may have” -> “is cumbersome, and may deliver”

Reply №17: Corrected.

18. Lines 62-63: “non-compliance with generally accepted measurement recommendations”: delete.

Reply №18: Corrected.

19. Lines 63-64: “and many more”: delete.

Reply №19: Corrected.

20. Lines 64-65: “Thus, there is a need for simple, non-invasive wireless monitoring systems that can solve some of these problems, allow wider” -> “Thus, non-invasive wireless monitoring systems are an appealing development, helping to address some of these limitations, and allowing a wider”

Reply №20: Corrected.

21. Lines 69-72: please substitute “PTT” and “PPG” with full-wording.

Reply №21: Corrected.

22. Line 71: “One study used the…”: please cite this study at the end of this sentence.

Reply №22: Corrected.

23. Line 72: “recording ECG and” -> “recording of ECG and”

Reply №23: Corrected.

24. Lines 73-75: please correct and improve the English in these sentences (i.e., reformulate them in correct English).

Reply №24: Corrected.

25. Line 76 (“validate a method”): which one? You mention above that "there are variable models" (lines 70-71) and that the CardioQVARK device was already used in "one study" (lines 71-72). Which other device did you aim to validate?

Reply №25: Huawei device.

26. Line 80: “It is a prospective cohort study”:
    • -> “This is a prospective…”
    • Why cohort study? I have the impression you just validated the device, against standard methods, in all participants (subdivided in various blood pressure categories). You did not compare two cohorts. Thus, this is rather a prospective, observational study. Not a cohort study. Modify this sentence into: “This is a prospective observational study conducted…”

Reply №26: Corrected.

27. Line 87 (“167 subjects, 64 women and 102 men between 18 and 88 were recruited”): this should belong (and must be moved) to the section Results. Here, you should state how many patients/probands you were aiming to recruit, and how this number was calculated (I guess, you decided the sample size according to the IEEE recommendations). In the Discussion section, you should add that this number was slightly lower than the sample size currently recommended (n=185) by the very recent ESH recommendations[Stergiou GS et al, J Hypertens, 2023 doi: 10.1097/HJH.0000000000003483.]. 

Reply №27: The sample size was determined according to the IEEE Standard for Wearable, Cuffless Blood Pressure Measuring Devices [EEE Standard for Wearable, Cuffless Blood Pressure Measuring Devices. The Institute of Electrical and Electronics Engi-neers, Inc, IEEE Standards Association, IEEE Engineering in Medicine and Biology Society. Standards Committee Institute of Electrical and Electronics Engineers, Incorporated, 2014. PDF: ISBN 978-0-7381-9213-0. Total pages 24].

28. Line 88: “medications in force were” -> “medications were”

Reply №28: Corrected.

29. Table 1: move Table 1 to the section Results.

Reply №29: Corrected.

30. Table 1:
    • “criteria” -> “characteristic”
    • Lines “Age>60”, “Age>75”, “Age<40”: most importantly, provide mean and SD (if normally distributed) or median and IQR (if non-parametrically distributed). Numbers in (arbitrarily chosen) discrete categories (of this continuous variable) are optional (you might keep them if you want to, or delete them if you prefer, I don't care). - Age median 66 years [59.5; 73]
    • “LV DD of 2 and 3 grade”: reformulate in correct Engish
    • “Vessel wall stiffness”: how was vessel wall stiffness assessed? (e.g.: pulse-wave velocity, flow-mediated dilation, AASI, pulse pressure, biomarkers of endothelial function, …) This must be explained in the Methods section.

Reply №30: Corrected.

-Lines “Age>60”, “Age>75”, “Age<40”: most importantly, provide mean and SD (if normally distributed) or median and IQR (if non-parametrically distributed). Numbers in (arbitrarily chosen) discrete categories (of this continuous variable) are optional (you might keep them if you want to, or delete them if you prefer, I don't care). - Age median 66 years [59.5; 73]

31. Line 96 (“At the first stage of the study observers training was provided”): reformulate in better English.

Reply №31: Corrected.

32. Line 98: “apparatus” -> “device”

Reply №32: Corrected.

33. Line 100: what dose “HBS” stand for? Reformulate in full words.

Reply №33: Corrected.

34. Line 104: “30 sec” -> either “30 seconds” or “30 s”

Reply №34: Corrected.

35. Lines 110-111: “the mean values of the two observers were used as reference measurements.” -> “the mean value of the two observers was used as reference.”

Reply №35: Corrected.

36. Lines 115, 124, 200, …: “PPG” -> “photoplethysmography”

Reply №36: Corrected.

37. Table 2: Nice table! However, this belongs to the section Results. Please move it there.

Reply №37: Corrected.

38. Line 137: “IEEE” -> “Institute of Electrical and Electronics Engineers”
    • There are standards, for example, from the European Society of hypertension[Stergiou GS et al. European Society of Hypertension recommendations for the validation of cuffless blood pressure measuring devices: European Society of Hypertension Working Group on Blood Pressure Monitoring and Cardiovascular Variability. J Hypertens. 2023. doi: 10.1097/HJH.0000000000003483.], which should have been considered as well. Indeed, IEEE is a technology association, while in clinical medicine (especially if you aim at proposing a screening method) it is pivotal to also include clinical considerations. Do the recommendations from IEEE align with the ones of ESH? If you look at the ESH paper, Table 4, you will notice that the current ESH recommendations are slightly stricter than the IEEE standards. Globally, it looks like that for most aspects (and at least looking at the whole group of patients) the tested device satisfies also these most stringent criteria (mean BP difference <5mmHg±8mmHg, although I did not verify whether this holds true also for all subgroups), and this should be stated (it strengthens your study). Please revise your Discussion taking these recommendations (number of subjects to include, reference method, accepted BP difference, …) into account and discuss these aspects.

Reply №37: Corrected.

39. Lines 139-140: “measurements of cuffless method. Mean” -> “measurements. Mean”

Reply №39: Corrected.

40. Lines 153-154: “61.1% were males.” –> “61.1% were males (Table 1).”

Reply №40: Corrected

41. Line 157: “sphygmomanometer. The mean…” -> “sphygmomanometer (Table 2). The mean…”

Reply №41: Corrected.

42. Lines 160-162: “The aim of this paper is to validate a method for non-invasive blood pressure measurement method based on the IEEE Standard for Wearable Cuffless Blood Pressure Devices. This standard has two-phase” -> “The IEEE Standard for Wearable Cuffless Blood Pressure Devices foresees a two-phase”

Reply №42: Corrected.

43. Line 168: what does “BHS” stand for?

Reply №43: BHS - British Hypertension Society (BHS) protocols [26.            O’Brien, E., Petrie, J., Littler, W. A., de Swiet, M., Padfield, P. D., Dillon, M. J., et al., Blood pressure measurement: recommen-dations of the British Hypertension Society, 2nd ed., London: BMJ Publishing Group; 1997.

O’Brien, E., Petrie, J., Littler, W., and de Swiet, M., “The British Hypertension Society protocol for the evaluation of blood pressure measuring devices,” Journal of Hypertension, vol. 11, no. suppl 2, pp. S43-S62, 1993].

44. Line 177: “the SBP and DBP values” -> “the SBP values”

Reply №44: Corrected.

45. Line 179: “based on a cuff (Figure 2, Figure 3, Figure 4, Figure 5).” -> “based on a cuff , without any trend over the range of included BP values (Table 4, Figures 2 and 3), while the DBP values were slightly but statistically significantly lower (mean bias -1.02 (95%-CI -1.65 to -0.38)) (Table 4, Figures 4 and 5).”

Reply №45: Corrected.

46. Line 182 (“The resulting raw MD composed -0.05”): what do you mean with “composed”? Please check and correct the English of this sentence.

Reply №46: Corrected.

47. Line 186 (“Density is a bit bimodal”): either it showed a bimodal distribution or not (it cannot be “a bit bimodal”). Please decide (either “density plots suggested a bimodal distribution” or “density plots suggested a roughly normal distribution”: since just one bar is lower between 2 “tall” histograms, I am personally not that sure this can be called a bimodal distribution) and reformulate accordingly.

Reply №47: Corrected. Modified change in discussion section.

48. Lines 191-192: although such a difference is likely irrelevant from a clinical perspective, this is a systematic, significant bias of the estimation, and should be reported as such in the body of the manuscript. This is even more important if you propose this technique as a screening method (which is a wrong conclusion), because even such small differences may have epidemiological relevance (on a population scale).

Reply №48: Corrected.

49. Line 198: “provides” -> “is a valuable initiative, since it has the potential of achieving”

Reply №49: Corrected.

50. Line 201: “taken in large sample” -> “taken in a large sample”

Reply №50: Corrected.

51. Line 203: “using standards of” -> “according to the standards of”

Reply №51: Corrected.

52. Lines 205-206: “that minimized our study limitations” -> “overcoming some of the limitations of our previous study [24].”

Reply №52: Corrected.

53. Line 207: “values definite by” -> “measurements of”

Reply №53: Corrected.

54. Line 208: “and for DBP was” -> “while for DBP it was”

Reply №54: Corrected.

55. Lines 211-216: reformulate in better, correct English.

Reply №55: Corrected.

56. Lines 217-219: This partly repeats lines 211-216. Please consider deleting these lines.Additionally (Line 218): "the most accurate (...) BP": SBP or DBP?

Reply №56: Corrected.

57. Line 223: “It can be used” -> “It could be used”

Reply №57: Corrected.

58. Line 224: “In this case, the patient” -> “The great advantage and appeal of such a method is that the patient”

Reply №58: Corrected.

59. Line 224: “need an additional” -> “need any additional”

Reply №59: Corrected.

60. Lines 224-225: “only mobile phone” -> “only a smart phone”

Reply №60: Corrected.

61. Line 228: “corruption”: this is the wrong word. Reformulate in better English (e.g. bias, confounding, modification, …).

Reply №61: Corrected.

62. Limitations (current lines 226-228) and Conclusions (current lines 229-232):Both in Limitations and Conclusions, you should discuss the significant bias of agreement detected for DBP. This is clinically probably not relevant, but might have epidemiological implications, especially if this method would be used for screening purposes (in research on salt-sensitive hypertension and on treatment of arterial hypertension, respectively in epidemiological studies aiming at determining BP cut-off values, such small differences have shown to potentially have a significant public health impact). Although you meet the requirements of IEEE, this result demonstrates that diastolic-only hypertension might be overseen, so that this method is not be suitable for screening. This is indeed a very important conclusion that you must transparently report and discuss.

Reply №61: Chapter limitations and conclusions have been modified according to comments.

 

Reviewer 3 Report

Comments and Suggestions for Authors

In their manuscript entitled "Practical Application of the New Cuffless Blood Pressure Measurement Method, Gogiberidze, et al, describe validation of the CardioQVARK device, a plethysmographic blood pressure (BP) monitoring system. Data generated from the device were compared to measurements by two trained technicians using a sphygmomanometer according to methods recommended by the IEEE Standard for Wearable Cuffless Blood Pressure Devices. The mean absolute difference for systolic BP was 3.44 ± 2.5 mmHg and for diastolic BP was 3.21 ± 2.82 mmHg, satisfying criteria for accuracy using the IEEE standards. The study is of importance in demonstrating the accuracy of a cuffless plethysmographic device in measuring BP. The methods are reasonable and are described in adequate detail. The manuscript could be improved by addressing the following issues:

1) Graphs should be enlarged so that they are legible.

2) A citation for the IEEE Standard for Wearable Cuffless Blood Pressure Devices should be provided.

3) In the Introduction, it is stated that the "the BP devices currently in use are usually based on the manometry method". Most monitors used in the US are oscillometric devices.

4) In the Discussion, it is stated the "Developing cuffless technologies for remote monitoring of BP provides better control of BP". This reviewer knows of no high-quality evidence supporting this assertion. If such evidence exists, it should be cited. If not, the statement should be modified.

 

Comments on the Quality of English Language

In their manuscript entitled "Practical Application of the New Cuffless Blood Pressure Measurement Method", Gogiberidze, et al, describe validation of the CardioQVARK device, a plethysmographic blood pressure (BP) monitoring system. Data generated from the device were compared to BP measurements by two trained technicians using a sphygmomanometer according to methods recommended by the IEEE Standard for Wearable Cuffless Blood Pressure Devices. The mean absolute difference for systolic BP was 3.44 ± 2.5 mmHg and for diastolic BP was 3.21 ± 2.82 mmHg, satisfying criteria for accuracy using the IEEE standards. The study is not particularly novel but is of importance in demonstrating the accuracy of a cuffless plethysmographic device in measuring BP. The results are valuable for future investigators or clinicians interested in using this device. The methods are reasonable and are described in adequate detail. The conclusions are reasonable. Several important but addressable suggestions were included with the Comments to the Authors.

 

Author Response

Reviewer 3 wrote that:

1. Graphs should be enlarged so that they are legible.

Reply №1: Corrected.

2. A citation for the IEEE Standard for Wearable Cuffless Blood Pressure Devices should be provided.

Reply №2: Corrected.

3. In the Introduction, it is stated that the "the BP devices currently in use are usually based on the manometry method". Most monitors used in the US are oscillometric devices.

Reply №3: Corrected.

4. In the Discussion, it is stated the "Developing cuffless technologies for remote monitoring of BP provides better control of BP". This reviewer knows of no high-quality evidence supporting this assertion. If such evidence exists, it should be cited. If not, the statement should be modified.

Reply №4: We have changed the discussion chapter. Cuffless blood pressure measurement devices are emerging as a convenient and tolerable alternative to cuff-based devices [Evaluation of the Accuracy of Cuffless Blood Pressure Measurement Devices: Challenges and Proposals. Ramakrishna Muk-kamala, Mohammad Yavarimanesh, Keerthana Natarajan, Jin-Oh Hahn, Konstantinos G. Kyriakoulis, Alberto P. Avolio and George S. Stergiou. Hypertension. 2021;78:1161–1167 https://doi.org/10.1161/HYPERTENSIONAHA.121.17747]. However, there are several limitations to cuffless blood pressure measurement devices that should be considered. For instance, the accuracy of cuffless blood pressure measurement devices are still being evaluated, and there remain challenges in ensuring the accuracy of such devices [Cuffless Blood Pressure Devices. Corey K Bradley, Daichi Shimbo, David Alexander Colburn, Daniel N Pugliese, Raj Pad-wal, Samuel K Sia, and D Edmund Anstey. Am J Hypertens. 2022 May; 35(5): 380–387. doi: 10.1093/ajh/hpac017]. Overall, cuffless blood pressure monitoring devices may improve adherence to blood pressure monitoring practices and provide a more convenient alternative to cuff-based devices. However, the accuracy and limitations of these devices should be considered when evaluating their use in the diagnosis and treatment of hypertension [Challenges Presented by Cuffless Measurement of Blood Pressure if Adopted for Diagnosis and Treatment of Hypertension. Alberto Avolio; James Cox; Kyrollos Louka; Fatemeh Shirbani; Isabella Ta; Ahmad Qasem; Mark Butlin. Pulse (2022) 10 (1-4): 34–45. https://doi.org/10.1159/000522660.].

 

Round 2

Reviewer 2 Report

Comments and Suggestions for Authors

 

The Authors have addressed some of my previous comments, and the manuscript has improved. However, Authors did not satisfactorily address three of the four main issues I outlined in my previous report: 1) the conclusions are still not completely consistent with the obtained results, 2) the Authors do still not acknowledge the limitation of having used the old IEEE recommendations instead of the current, most recent ESH recommendations on BP device validation (this is probably because, although this manuscript was submitted in Autumn 2023, the study was performed 2020-2021: this limitation must be explicitely acknowledged), 3) the importance of this new device is still overstated (in particular, Authors exaggerate purported problems or limitations of the oscillometric method: the interest of the CardioQVARK is its easy of use and portability, not a problem with the oscillometric method).

There are still numerous requests that need to be addressed.

 

 

Page 1, line 28 and line 41: “average”: average is an ambiguous word: please modify into either “mean” or “median”, whatever applies.

 

Page 1, line 35: how can a “standard lead I” be measured if the used ECG had just one lead? The standard extremity lead I needs 4 electrodes (otherwise it is just “a lead”, like for example on a ECG monitor on an intensive care unit, but not “the standard lead I”). Please reformulate.

 

Page 4, lines 169-170, and then lines 171-172: same comment and request.

 

Page 1, lines 40-41: “with this method”: delete.

 

Page 2, lines 58-61 (“The difference...” up to “…for arterial hypertension.”): delete.

 

Page 2, lines 77-78: no, this is not true. Arterial hypertension is the strongest risk factor for stroke, while smoking is the strongest risk factor for acute myocardial infarction.

 

Page 2, line 86: it is not true that the oscillometric BP measurement is cumbersome. The oscillometric method is easy, rapid, reproducibile, and mostly delivers accurate measurements, at the point that it has been validated. The point is that it is not as easy as an smartphone at home. Once again, please do not “understate” the standard method in an attempt to “overstate” the interest of your new method. Your new method is interesting and very practical, this is its interest and strength. This is sufficient to make it interesting (even if the oscillometric method is already good).

 

Page 2, line 89 (“standard calibration”): again, this is not true. Delete.

 

Page 2, line 89: “Thus”: delete.

 

Page 2, lines 91-92: “could address some of these limitations by offering a wider application” -> “could offer a wider application”

 

Page 3, lines 115-117 (“We have developed..” up to “..pulse waves”): delete.

 

Page 4, line 124: the study was performed between 2020 and 2021. What happened between November 2021 and October 2023? Why this delay?

 

Page 4, lines 136-138: the definition of “compensated high blood pressure” is still unclear. Please reformulate in better, understandable English.

 

Page 4, lines 179-180: “were presented in our previous manuscript [24].” -> “have been previously reported [24].”

 

Page 8, lines 199-201: Please read and address my previous request, and modify the manuscript accordingly. You must develop your statistical analysis plan, you cannot borrow this from recommendations (of course, you can (and probably should) develop your statistical analysis plan basing on such recommendations).

 

Page 8, lines 210-211: the previous version was correct, the new version modifies the meaning and is not correct. One has to pay attention, because the professional translating services do not always understand the medical background and sometimes correct in an incorrect way.

The correct version should be: “were calculated for MAD ≤5, ≤10 and ≤15mmHg”.

 

Page 8, lines 227-229: delete.

 

Page 8, line 229: “anticipates”: "foresees" was correct, "anticipates" is wrong. Please correct this back.

 

Page 9, lines 239-245: Was this assessed? If yes, provide the results. Currently, Table 1 just reports the number of patients in whom this was measured, but not their PWV.

 

Page 9, Table 1, “Vessel wall stiffness”: same comment. This is just the number of patients in whom this was assessed. Please provide the result (median and IQR or mean and SD, PWV in m/s).

 

Page 9, Table 2, Title: “Blood pressure level in cohort patients.” -> “Blood pressure in cohort patients.”

Furthermore, please add: “…cohort patients as measured with ...” (please state whether these values refer to the oscillometric or the new device measurement).

 

Page 11, Table 4: are the values between square brackets (e.g. [3.05, 3.82]) absolute or interquartile range? Please specify (either in the table title or in a footnote).

 

Page 12, Figure 2: What do the shaded black lines represent? By eye, it looks like this may be +/- 8mmHg? If this is the case, why 8mmHg / how was this chosen? (The old IEEE recommendations requested 7mmHg, the new ESH recommendation request 5mmHg… why 8mmHg?)

 

Page 13, line 293: “limitations in our previous” -> “limitations of our previous” ("of" was correct, "in" is wrong: please correct this back.)

 

Page 14, line 317: “his study” -> “this study”

 

Page 14, lines 319-322: modify into: “The difference was very small and unlikely to be of clinical relevance for the individual patient, but this may well have epidemiological relevance on a population level. Therefore, the CardioQVARK device, while being worthwile for monitoring of patients over time, may not be suitable for screening purposes.”

 

Page 14, line 327: “to screen for arterial hypertension”: No! Your results demonstrate the opposite! Please be consistent with your own results! Science must be honest and consistent. The Bland-Altman analysis on DBP demonstrates that this device, while adequate for monitoring BP over time (as demonstrated by your other results and by the small, albeit significant, error in measuring DBP), is not suited for screening.

 

Page 14, lines 332-336: modify into: “For instance, this study showed a high proportion of measurements with a measurement error <5mmHg, while detecting a small, although statistically significant, bias in the measurement of diastolic blood pressure. This suggests that this device may not be suitable for screening purporses. However, its value for monitoring of BP over time is confirmed. Furthermore and most importantly, the easy measurement and the device portability (integrated in a smartphone) may increase self-awareness of hypertensive patients and, potentially, lead to an improved adherence to their treatment.”

 

Page 14, paragraph Limitations (lines 339-344): The main limitation is that (this study being performed between 2020 and 2021), you applied the old IEEE protocol, instead of the current (2023) ESH recommendations. This must be cited as a limitation, as previously already requested.

 

Page 15, lines 348-349 (“The results indicate that the described method can be applied in clinical practice.”): delete.

 

References #31, 32, 33, 34 are currently not reported according to the layout requested by the journal. Please report them as per Authors instructions (first the Authors’ names, then the title, as you are correctly doing for references #1 to #30).

 

Comments on the Quality of English Language

Please see above.

Author Response

Please see the attachment.

 

Author Response File: Author Response.pdf