In Vivo Validation of a Cardiovascular Simulation Model in Pigs
, Jonas Gesenhues 2, Maike Stemmler 2, Marc Hein 1, Rolf Rossaint 1 and Mare Mechelinck 1Round 1
Reviewer 1 Report
This paper presents a validation of a lumped-parameter modeling approach against in-vivo animal modeling. The paper is very well-written and organized and thus deserve publication after addressing the following two minor comments.
page 1 line 30: please add the following references on computer modeling of VAD to support this statement.
[1] Scardulla, F., Pasta, S., D'Acquisto, L., Sciacca, S., Agnese, V., Vergara, C., Quarteroni, A., Clemenza, F., Bellavia, D., Pilato, M. Shear stress alterations in the celiac trunk of patients with a continuous-flow left ventricular assist device as shown by in-silico and in-vitro flow analyses
(2017) 36 (8), pp. 906-913.
[2] Scardulla, F., Bellavia, D., D'Acquisto, L., Raffa, G.M., Pasta, S. Particle image velocimetry study of the celiac trunk hemodynamic induced by continuous-flow left ventricular assist device
(2017) 47, pp. 47-54.
page 4 line 159: the lumped parameter model here proposed does not take into account that the left ventricle is deformable. In the setting of VAD, the septum of the left ventricular wall may lead to a paradoxical leftward shift of the interventricular septum that can determine the collapse of the septum into the left ventricular chamber and ultimately heart failure. The lumped-parameter model could be coupled with additional equations to include a deformable LV wall as done in literature by the group at Maastricht university that realease the open-source software CircAdapt. Please add an explanation on the assumption and related limitations on having a rigid ventricular wall in the present lumped-parameter approach.
Author Response
Please see the attachment.
Author Response File: 
Author Response.pdf
Reviewer 2 Report
- Mathematical expressions should be correctly typed and described. E.g., line 146. " λ [P_ED = P0_ES*(exp(λ(V_ED-V0))-1]" should be typed as a mathematical expression.
- Section 2.2. The model is not presented properly. In what way do we obtain dynamic behavior in the model like in Fig. 3? As far as I know, in order to get Fig.3, we need some differential equations for such a model.
- Where are the simulations? I mean the curves simulating the dynamic changes of the parameters.
Author Response
Please see the attachment.
Author Response File: Author Response.pdf
Reviewer 3 Report
The authors simulate cardiac dynamics in pig models using a numerical model. Although as an idea it is interesting and there is certainly need for numerical models which can simulate cardiac dynamics accurately, fundamental problems in the manuscript show that the authors do not have a deep understanding of how these numerical models work.
Thew authors show varying elastance atrial models in Figure 2. However, ventricular pressure and volume signals clearly show that atria were modeled with constant elastance. Otherwise, effects of atrial contraction should have been seen in the ventricular signals as well.
Left and right compartments in Figure 2 include left and right atria. Atria are not ventricles and must be labelled explicitly.
The authors do not present how did they tune the parameters to simulate cardiac dynamics in pigs. There are plenty of optimization algorithms in the literature. They can choose one of them and optimize the parameter set in the numerical model to minimize discrepancies between the numerical results and experimental data.
There are also too many citations to the studies with LVADs. LVADs are devices supporting failing heart. The submitted study does not simulate LVAD support. It is about cardiac dynamics. Next stage can be optimizing the model for LVAD support. However, in the submitted form these papers seem a bit irrelevant.
Author Response
Please see the attachment.
Author Response File: Author Response.pdf
Round 2
Reviewer 1 Report
all comments and suggestions were properly addressed. the paper deserves publication in my opinion
Reviewer 2 Report
All my comments were addressed in the revised version
Reviewer 3 Report
The response from the authors is far from convincing the reviewer about the validity of the results. Mitral valve flow rate and left atrial pressure signals presented in the cover letter clearly show that there is no atrial contraction in the model. The authors have to correct their model to simulate atrial contraction as in mentioned in the manuscript or modify their manuscript to acknowledge the fact that there is no atrial contraction. Only constant compliance or elastance used in the atria. In the submitted form presented results and text contradict. Anyone specialized in this field can see this. Therefore, the paper must be rejected.
