A Closed-Loop Modeling Framework for Cardiac-to-Coronary Coupling.

The mechanisms by which cardiac mechanics effect coronary perfusion (cardiac-to-coronary coupling) remain incompletely understood. Several coronary models have been proposed to deepen our understanding of coronary hemodynamics, but possibilities for in-depth studies on cardiac-to-coronary coupling are limited as mechanical properties like myocardial stress and strain are most often neglected. To overcome this limitation, a mathematical model of coronary mechanics and hemodynamics was implemented in the previously published multi-scale CircAdapt model of the closed-loop cardiovascular system. The coronary model consisted of a relatively simple one-dimensional network of the major conduit arteries and veins as well as a lumped parameter model with three transmural layers for the microcirculation. Intramyocardial pressure was assumed to arise from transmission of ventricular cavity pressure into the myocardial wall as well as myocardial stiffness, based on global pump mechanics and local myofiber mechanics. Model-predicted waveforms of global epicardial flow velocity, as well as of intramyocardial flow and diameter were qualitatively and quantitatively compared with reported data. Versatility of the model was demonstrated in a case study of aortic valve stenosis. The reference simulation correctly described the phasic pattern of coronary flow velocity, arterial flow impediment, and intramyocardial differences in coronary flow and diameter. Predicted retrograde flow during early systole in aortic valve stenosis was in agreement with measurements obtained in patients. In conclusion, we presented a powerful multi-scale modeling framework that enables realistic simulation of coronary mechanics and hemodynamics. This modeling framework can be used as a research platform for in-depth studies of cardiac-to-coronary coupling, enabling study of the effect of abnormal myocardial tissue properties on coronary hemodynamics.