We propose an integrated electromechanical model of the human heart, with focus on the left ventricle, wherein biophysically detailed models describe the different physical phenomena concurring to the cardiac function. We model the subcellular generation of active force by means of an Artificial Neural Network, which is trained by a suitable Machine Learning algorithm from a collection of pre-computed numerical simulations of a biophysically detailed, yet computational demanding, high-fidelity model. To provide physiologically meaningful results, we couple the 3D electromechanical model with a closed-loop 0D (lumped parameters) model describing the blood circulation in the whole cardiovascular network. We prove that the 3D-0D coupling of the two models is compliant with the principle of energy conservation, which is achieved in virtue of energy-consistent boundary conditions that account for the interaction among cardiac chambers within the computational domain, pericardium and surrounding tissue. We thus derive an overall balance of mechanical energy for the 3D-0D model. This provides a quantitative insight into the energy utilization, dissipation and transfer among the different compartments of the cardiovascular network and during different stages of the heartbeat. In virtue of this new model and the energy balance, we propose a new validation tool of heart energy usage against relationships used in the daily clinical practice. Finally, we provide a mathematical formulation of an inverse problem aimed at recovering the reference configuration of one or multiple cardiac chambers, starting from the stressed configuration acquired from medical imaging. This is fundamental to correctly initialize electromechanical simulations. Numerical methods and simulations of the 3D-0D model will be detailed in Part II.
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