Structure (Epicardial Stenosis) and Function (Microvascular Dysfunction) That Influence Coronary Fractional Flow Reserve Estimation^†

Round 1

Reviewer 1 Report

I believe that the topic is too specific for many readers. I suggest to try to simply explanation

Author Response

Please see attached file.

Author Response File: Author Response.pdf

Reviewer 2 Report

The study proposes a detailed description of the coronary vasculature that allows fast estimation of coronary FFR and test it on different conditions such as focal stenosis and diffuse stenosis. 
The study is nice, but there are many assumptions that lies in the mathematical equation. So, I am not sure if the author claims that heart rate may not affect the index based on sensitivity analysis is sufficient. I humbly suggest the authors reconsider this statement or elaborate more on the limitation. 

Methods
Provide citations for the assumption of blood viscosity, density, and elasticity. Blood density should not be the same as water. 

I would like to suggest the authors to split the discussion with the conclusion. The author makes a statement at the end of the abstract that “The independence of the index with respect to heart rate suggests that computationally inexpensive steady-state simulations may provide sufficient information to reliably compute the index.” I think it will be interesting to discuss more on how the effect of unsteady-state simulation is not significant in this modelling and how different these findings compare to the published literature. 

Minor review 
 intertia in line 110 should change to inertia 

Author Response

Please see attached.

Author Response File: Author Response.pdf

Reviewer 3 Report

The authors simulate coronary stenosis microvascular disease and estimate fractional flow reserve using a lumped parameter model. Although simulation results are promising clinical applicability of such a model may remain limited.

How will the authors ensure that parameter values used in the simulations are patients specific and the simulations will be accurate?

It looks like they need clinical images of at least measurements for vessel diameters. Moreover, cardiac parameters and parameters for systemic and pulmonary circulations should also be estimated according to the diagram given in Figure 1.

In this case the numerical models simulating ventricular and atrial functions are also important. However, it looks like pulsatility is provided by the variable resistances at the end of each coronary compartment. How will the authors relate cardiac parameters with the impedance of each compartment? If they have measurements and images, then why would someone need such a simulation?

Again, the authors state that “The inclusion of autoregulatory processes will further assist to make the model’s FFR estimates quantitatively reliable”. Increasing models complexity may make the model more difficult to simulate patient specific blood flow and pressures. What type estimation or optimisation method can be utilised to estimate patients specific variables in such a model?

Author Response

Please see attached.

Author Response File: Author Response.pdf

Round 2

Reviewer 2 Report

I am happy with the manuscript after the revisions. recommend to accept. 

Reviewer 3 Report

The authors responded to the reviewer's comments sufficiently. The submitted manuscript can be accepted as a publication.