I have not seen anything in the literature about significant cardiac changes associate with women in their 30s and 40s, but as cardiologists and OBGYNs are beginning to really collaborate, we will understand more about these patients. Based on what these data say, I'll have to consider whether I should account for these patients at the hemodynamics level, cell signaling level, or somewhere in between.

Thank you I actually did not use a Finite element model for this study - instead I used the compartmental model, where we treat the Left and right ventricles as thin-walled spheres with a cavity volume and wall thickness. I think that moving forward, adding complexity to my model will be more focused on the intracellular signaling pathways both because this is where we need the details and also to save computational time.

Thank you! I have not investigated the role of obesity - but would be interested in expanding my models into these context in the future.

I don't know which nodes will be different between these patients yet - Most of the studies I have found so far focus mostly on estrogen and its effects on heart failure. Less studies have studied the effects on pregnancy.

Thank you! Right now, the smaller scale network model is pretty sensitive to the input parameters because there are not too many species interacting. Sensitivity will really come into play once we have more connections and interactions. How sensitive the model will be to individual inputs will depend on how connected a specific species is. In terms of inherent variation in the biological response, I think that conducting a sensitivity analysis will be key for understanding which variations we should care about and incorporate into the simulations.

Thank you, Andrew! I think this model would be great for understanding sex differences and hypertrophy. In fact, I think I will have better luck incorporating estrogen signaling into the model because most of the experimental studies report the effects of estrogen, not progesterone. Applying these models within the gender difference context might be an important intermediate step before pregnancy.

Hi Jacob, we use MATLAB for running these simulations. The compartmental model is essentially a system of ODEs. The network model is generated using Netflux (https://github.com/saucermanlab/Netflux). Right now, simulating 21 days of growth takes about 5 minutes.

Right now, we use a linear mapping between stretch calculated by the mechanical model into "Stretch" input into the network model - so NetworkStretch = m*MechStretch + b. I tuned the slope (m) and intercept (b) to the Volume overload study.