“Vox Populi” Fractional Flow Reserve (vpFFR)—Leveraging Wisdom of the Crowd for the Assessment of Hemodynamic Severity of Intermediate Coronary Lesions

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

The authors propose a novel concept of “vox populi FFR” (vpFFR), derived from the collective predictions of five interventional cardiologists, and compare its diagnostic performance against 2D- and 3D-QCA using invasive FFR as the reference. The study is conceptually innovative and addresses an important clinical question regarding non-invasive physiological assessment of coronary lesions. However, several methodological and analytical limitations currently hinder the strength and generalizability of the conclusions.

 

Major

1. Methodological Transparency and Reproducibility: Line 112-120. The process of vpFFR derivation lacks sufficient detail. It is unclear whether predictors were completely blinded to clinical data, whether they received any training or calibration, and whether their assessments were truly independent. A standardized workflow diagram or checklist should be provided to enhance reproducibility.
2. The use of only Pearson correlation is insufficient to assess agreement between vpFFR and FFR. Bland-Altman analysis and intraclass correlation coefficients (ICC) should be included to evaluate bias and consistency.
3. ROC analysis should report the optimal cut-off value for vpFFR along with corresponding sensitivity, specificity, and likelihood ratios.
4. While vpFFR outperforms QCA, its performance (AUC 0.78) is modest and comparable to some angioFFR software in real-world settings. The manuscript should more critically discuss whether vpFFR truly serves as a clinically meaningful “benchmark” or rather as a “human-performance reference” for validating computational models.
5. The limitations are understated. Important issues such as single-center design, potential observer bias, lack of inter-/intra-observer variability assessment for vpFFR, and the high proportion of trainees among predictors should be discussed in depth, along with their impact on generalizability.

 

Minor

1.Some sentences are lengthy and complex. Consider revising for conciseness (e.g., in the Introduction and Discussion).

2.Ensure all acronyms are defined at first use (e.g., ORBITA in the Discussion).

Author Response

Please see the attachment

Author Response File: Author Response.pdf

Reviewer 2 Report

Comments and Suggestions for Authors

Hello,

Thanks for submitting this manuscript ' "Vox populi" Fractional Flow Reserve (vpFFR) - A Novel Benchmark for FFR Surrogates" to this journal. I have following comments- 

1.It is an interesting concept on the line of CT-FFR derived estimation however the methodology of it's integration is not referenced adequately in the draft.

2. Unlike lesion assessment, vessels as evaluated in the method and this undermines the concept and represents a major drawback of the methodology. Why weren't the lesions compared instead of vessels ?

3. How was 5 assessments were arrived at for averaging the 2D and 3D QCA and not any other number ?

4. How was the sample size calculated ?

5. What were the procedural outcomes of the immediate interventions ?

6. What was the method of internal and external validation of the method ?

Thanks 

 

Author Response

Please see the attachment

Author Response File: Author Response.pdf

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

No further comments

Author Response

The reviewer had no further comments

Reviewer 2 Report

Comments and Suggestions for Authors

Hello,

Thanks for revising the manuscript. 

However 2 small queries still remain

1. In tandem lesion there are papers that have defined FFR for lesions separately as well. Hence the lesion specific assessment can be done rather than vessel specific assessment. Mention this as limitation of the study
2. Mention that 5 assessment of vpFFR is arbitrary and is not based on any scientific evaluation and the method is neither internally or externally validated 
3. Mention need for larger and more refined assessment methodology with more scientific vigor for further evaluation in the draft. Thanks 

Author Response

1. In tandem lesion there are papers that have defined FFR for lesions separately as well. Hence the lesion specific assessment can be done rather than vessel specific assessment. Mention this as limitation of the study

We thank the reviewer for this comment and have mentioned this in the limitations (line 328).

2. Mention that 5 assessment of vpFFR is arbitrary and is not based on any scientific evaluation and the method is neither internally or externally validated 

We thank the reviewer for this comment and have mentioned this in the limitations (line 333-334)

3. Mention need for larger and more refined assessment methodology with more scientific vigor for further evaluation in the draft. Thanks 

We thank the reviewer for this comment and have mentioned this in the limitations (line 336-339)