Optimization of Long Superficial Femoral Artery Percutaneous Transluminal Angioplasty by Intraoperative Doppler Ultrasound

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

Introduction

Line 102 contains an amazing statement because of the availabliity and non-ivasive character of the DUS technique. A short survey of Pubmed confirms this, thereby affirming the importnace of the topic. 

The introduction should end with a clear research question as sated in line 114-115

Table1: Rutherford classification is limited to I, IIa, IIb and III - this should be modified 

Table 2: the meaning of following data (procedural details) is unclear 

   Pre-dilatation 62 (100)

   Post dilatation 37 (59.6)

The lines 268-269 contain a very important statement (..., one third of angiography-based successes should be reclassified as failures after intraoperative DUS assessment). It could be related to the statement in line 315 (Whether or not this this “functional-guided” optimization algorithm might impact positively on long-term outcomes should be investigated further). This outcome is what matters most. For this reason, the authors are encouraged to perform or at least recommend trials in this respect. 

Author Response

Dear Editor, dear Reviewers

please find below a point-to-point replay to your comments.

We have uploaded the revised manuscript with changes tracked in bold. I thank the reviewers for their very positive comments that will improve definitively the quality of the manuscript.

Reviewer #1 (Comments for the Author):

Introduction

Line 102 contains an amazing statement because of the availability and non-invasive character of the DUS technique. A short survey of Pubmed confirms this, thereby affirming the importance of the topic. 

Response: we are delighted that this reviewer has appreciated the objective of the study.

The introduction should end with a clear research question as sated in line 114-115

Response: we appreciated the insightful comment of this reviewer, and we concur this point must be emphasized. In the revised introduction paragraph, you can find the following statment: “the aim of the study was to evaluate whether intraoperative Doppler ultrasound (DUS) assessment of femoro-popliteal lesions that have undergone PTA allows for a more accurate definition of technical success compared to angiography”.

Table1: Rutherford classification is limited to I, IIa, IIb and III - this should be modified 

Response: we appreciated the comment of the reviewer, and we concur the Rutherford classification reported in the table one could have been misleading since we have reported the RC categories but don’t the grades. We have revised the table 1 reporting both, categories and grades.

Table 2: the meaning of following data (procedural details) is unclear 

   Pre-dilatation 62 (100)

   Post dilatation 37 (59.6)

Response: we concur that the data highlighted might be misleading. We have now specified that pre-dilatation and post dilatation referred to two actions taken to approach the target lesion. In other words, 100% of the lesions have been pre-dilated and 60% post dilatated.

The lines 268-269 contain a very important statement (..., one third of angiography-based successes should be reclassified as failures after intraoperative DUS assessment). It could be related to the statement in line 315 (Whether or not this this “functional-guided” optimization algorithm might impact positively on long-term outcomes should be investigated further). This outcome is what matters most. For this reason, the authors are encouraged to perform or at least recommend trials in this respect.

Response: we welcome the precious suggestion from this reviewer, and we have now modified the last sentence of the para 4.3 accordingly (Lines 315-17).

Reviewer 2 Report

Comments and Suggestions for Authors

Dear Authors,

Your manuscript Optimization of Long Superficial Femoral Artery Percutaneous Transluminal Angioplasty by Intraoperative Doppler Ultrasound presents an interesting approach to optimizing the percutaneous transluminal angioplasty procedure with intraoperative Doppler ultrasound. However, I believe the manuscript could benefit from several revisions to enhance its scientific impact and clinical relevance.

While the concept is intriguing, the current manuscript appears somewhat limited in demonstrating tangible clinical benefits. The clinical perspective section is highly valuable and provides significant insight.To strengthen your findings, I suggest emphasizing measurable clinical advantages of the proposed multi-imaging approach. For example, outcomes such as lower radiation exposure, reduced procedure costs, shorter procedure duration, or improved patient outcomes (e.g., reduced need for reinterventions or better vessel patency rates). The last two should be clearly addressed and visualized, perhaps through Kaplan-Meier analysis or similar outcome plots not only in the table. Including these data in the results section would greatly enhance the clinical impact of the study.

I recommend including the lesion TASC classification in Table 2 to further clarify the characteristics of the treated lesions. It would also be important to acknowledge in the limitations section that variations in lesion lengths may introduce bias in the outcome analysis. Additionally, the small sample size is a concern and should be more explicitly noted as a limitation.

The discussion would benefit from a more detailed comparison of intraoperative Doppler ultrasound with other imaging modalities, such as IVUS, CO2 angiography, or OCT. Highlighting the relative advantages and disadvantages of these approaches could provide readers with a clearer perspective on the clinical utility of your proposed method.

Although the conclusions are cautious and transparent, they underscore a key limitation of the study: the lack of conclusive evidence to support a significant change in clinical practice based on your findings. This is fair and reflects the current state of the data.

Overall, while the study is promising, the manuscript requires major revisions to fully justify the use of a multi-imaging approach in optimizing therapy efficacy. I look forward to reviewing a revised version that incorporates these suggestions.

Best regards,

Author Response

Dear Authors,

Your manuscript Optimization of Long Superficial Femoral Artery Percutaneous Transluminal Angioplasty by Intraoperative Doppler Ultrasound presents an interesting approach to optimizing the percutaneous transluminal angioplasty procedure with intraoperative Doppler ultrasound. However, I believe the manuscript could benefit from several revisions to enhance its scientific impact and clinical relevance.While the concept is intriguing, the current manuscript appears somewhat limited in demonstrating tangible clinical benefits. The clinical perspective section is highly valuable and provides significant insight.To strengthen your findings, I suggest emphasizing measurable clinical advantages of the proposed multi-imaging approach. For example, outcomes such as lower radiation exposure, reduced procedure costs, shorter procedure duration, or improved patient outcomes (e.g., reduced need for reinterventions or better vessel patency rates). The last two should be clearly addressed and visualized, perhaps through Kaplan-Meier analysis or similar outcome plots not only in the table. Including these data in the results section would greatly enhance the clinical impact of the study.

Response: Dear reviewer, thank you for your insightful and positive comments that will help to increase the quality of the manuscript definitively. We have now implemented a new figure (figure number 4) depicting the Kaplan Mayer curve for TVR.

Regarding the possibility to explore other relevant outcomes such as lower radiation exposure or reduced procedural costs, we totally agree that it would be of great interest for the readers, but it would be possible only in presence of a comparison arm that it is not the case in the present analysis. However, it could be the object of a new intriguing investigation focused on that. 

I recommend including the lesion TASC classification in Table 2 to further clarify the characteristics of the treated lesions.

Response: We concur with this reviewer that the TASC classification could be useful to clarify the lesion characteristics. The revised table 2 was implemented accordingly.

It would also be important to acknowledge in the limitations section that variations in lesion lengths may introduce bias in the outcome analysis.

Response: Although the mean lesion complexity is high as demonstrated by the fact that most of the attempted lesions are TASC >2, we concur with this reviewer that the variation in lesion length represents a potential bias in the outcome analysis and therefore it has now listed among the study limitations.

Additionally, the small sample size is a concern and should be more explicitly noted as a limitation.

Response: we concur that this issue is relevant as moreover highlighted by the other reviewer. It was now reported in the limitation paragraph.

The discussion would benefit from a more detailed comparison of intraoperative Doppler ultrasound with other imaging modalities, such as IVUS, CO2 angiography, or OCT. Highlighting the relative advantages and disadvantages of these approaches could provide readers with a clearer perspective on the clinical utility of your proposed method.

Response: we thank the reviewer for the comment. Although we concur that this aspect is very interesting, we have not expanded this point in the discussion for the word count limit.

Although the conclusions are cautious and transparent, they underscore a key limitation of the study: the lack of conclusive evidence to support a significant change in clinical practice based on your findings. This is fair and reflects the current state of the data. Overall, while the study is promising, the manuscript requires major revisions to fully justify the use of a multi-imaging approach in optimizing therapy efficacy. I look forward to reviewing a revised version that incorporates these suggestions.

We thank the reviewer for this thoughtful and wise consideration. However, in our opinion, despite the many limitations, the present study represents a small step towards a multi-imaging modality mindset which was demonstrated to play a crucial role in other field of cardiology. Furthermore, we concur the need for dedicated trails with larger simple size of patients to finally demonstrate if this approach has a clinical utility.

 

Round 2

Reviewer 2 Report

Comments and Suggestions for Authors

Dear Authors,

Your study presents an interesting approach to optimizing the percutaneous transluminal angioplasty procedure with intraoperative Doppler ultrasound. However, I believe the manuscript would benefit from further revisions to enhance its scientific impact and clinical relevance.

While the concept is intriguing, the manuscript currently lacks sufficient emphasis on tangible clinical benefits. To strengthen the findings, I recommend focusing on measurable advantages of the proposed multi-imaging approach. For example, outcomes such as reduced x-ray time, lower radiation exposure, reduced procedure costs, shorter procedure duration, or improved patient outcomes (e.g., reduced reinterventions or better vessel patency rates) should be highlighted. If additional data for these outcomes cannot be provided, a thorough discussion of their potential relevance should be included. In particular, the discussion section should elaborate on how intraoperative Doppler ultrasound compares to other imaging modalities such as IVUS, CO2 angiography, or OCT in terms of clinical utility and cost-effectiveness.

The Kaplan-Meier curve for TVR is a valuable addition but is currently of low image quality. I recommend improving its resolution and updating the time axis to show months instead of days for better clarity and interpretation. Additionally, please include Kaplan-Meier analyses stratified by TASC classes to provide deeper insights into how lesion characteristics may impact the outcomes. These results should also be discussed thoroughly in the manuscript.

Although the sample size is mentioned as a limitation, there is a typo in this section that should be corrected. The small sample size remains a critical concern and should be carefully discussed in terms of its impact on the study's statistical power and generalizability.

Lastly, while the conclusions are cautious and transparent, they should better align with the presented data. The current conclusions contain ideas for future research, which are interesting but speculative and lack sufficient supporting data. A rewrite of the conclusion section is necessary to more accurately reflect the results and limitations of the study this suggestion was totally neglected in the revised manuscript.

Overall, the study presents a promising concept, but major revisions are still required to fully address the limitations, improve clarity, and strengthen the clinical relevance of the findings. I look forward to reviewing a revised version that incorporates these suggestions.

Best regards,

Author Response

 

Your study presents an interesting approach to optimizing the percutaneous transluminal angioplasty procedure with intraoperative Doppler ultrasound. However, I believe the manuscript would benefit from further revisions to enhance its scientific impact and clinical relevance.

While the concept is intriguing, the manuscript currently lacks sufficient emphasis on tangible clinical benefits. To strengthen the findings, I recommend focusing on measurable advantages of the proposed multi-imaging approach. For example, outcomes such as reduced x-ray time, lower radiation exposure, reduced procedure costs, shorter procedure duration, or improved patient outcomes (e.g., reduced reinterventions or better vessel patency rates) should be highlighted. If additional data for these outcomes cannot be provided, a thorough discussion of their potential relevance should be included. In particular, the discussion section should elaborate on how intraoperative Doppler ultrasound compares to other imaging modalities such as IVUS, CO2 angiography, or OCT in terms of clinical utility and cost-effectiveness.

Response: We concur with the reviewer that this point is relevant; we have now elaborated that in the discussion paragraphs 4.2 e 4.3.

The Kaplan-Meier curve for TVR is a valuable addition but is currently of low image quality. I recommend improving its resolution and updating the time axis to show months instead of days for better clarity and interpretation. Additionally, please include Kaplan-Meier analyses stratified by TASC classes to provide deeper insights into how lesion characteristics may impact the outcomes. These results should also be discussed thoroughly in the manuscript.

Response: we thank the reviewer for the comment. We have modified the figure accordingly. However, we are confident this reviewer agrees that since the number of events occurred is very small (just 4), stratifying the KM curve by TASC classes could be not necessary.

Although the sample size is mentioned as a limitation, there is a typo in this section that should be corrected. The small sample size remains a critical concern and should be carefully discussed in terms of its impact on the study's statistical power and generalizability.

Response: we apologize for the typo. Furthermore, we have implemented the limitation paragraph underlining that the small sample size remains a critical concern.

Lastly, while the conclusions are cautious and transparent, they should better align with the presented data. The current conclusions contain ideas for future research, which are interesting but speculative and lack sufficient supporting data. A rewrite of the conclusion section is necessary to more accurately reflect the results and limitations of the study this suggestion was totally neglected in the revised manuscript.

Response: we thank the reviewer for the insightful comment. We have modified the conclusion accordingly

Overall, the study presents a promising concept, but major revisions are still required to fully address the limitations, improve clarity, and strengthen the clinical relevance of the findings. I look forward to reviewing a revised version that incorporates these suggestions.

Response: we thank this reviewer for the great support provided. All the positive comments have definitively contributed to increase the quality of the manuscript.

Best regards

Round 3

Reviewer 2 Report

Comments and Suggestions for Authors

Dear Authors,

Your study presents an interesting approach to optimizing the percutaneous transluminal angioplasty procedure with intraoperative Doppler ultrasound after major revision. However, I believe the manuscript would benefit from further minor revisions to enhance its scientific impact and clinical relevance.

Please, add data to the the Lesion and procedural characteristics table about the lesions requireing optimization and lesions not requiring too. Please, include Kaplan-Meier analyses stratified by lesions requiring optimization and lesions not requiring optimization to provide deeper insights into how US  may have impact the outcomes. 

The study presents an interesting concept, but minor revisions are still required to  strengthen the clinical relevance of the findings. I look forward to reviewing a revised version that incorporates these suggestions.

Author Response

Please, add data to the the Lesion and procedural characteristics table about the lesions requireing optimization and lesions not requiring too. Please, include Kaplan-Meier analyses stratified by lesions requiring optimization and lesions not requiring optimization to provide deeper insights into how US  may have impact the outcomes. 

Response. we have greatly appreciated the suggestion of this reviewer to stratify the KM analysis by lesions requiring optimization and lesions not requiring optimization. Accordingly, in the revised version of the manuscript you can find a new table comparing the lesion characteristics between optimization and non-optimization group and a new KM figure (figure 4).

Thank you very much for the great support.