Abstract

Simulating cardiac electromechanical function is one of the most striking examples of a successful integrative multi-scale modeling approach applied to a living system directly relevant to human disease. Today, thanks to nearly fifty years of research in the field and the rapid progress of high-performance computing, we stand at the threshold of a new era: anatomically-detailed tomographically-reconstructed models that integrate from the ion channel or sarcomere to the electromechanical interactions in the intact heart are being developed. Such models, while still in its infancy, hold high promise for interpretation of clinical and physiological measurements in terms of cellular mechanisms; for improving the basic understanding of the mechanisms of dysfunction in disease conditions, such as reentrant arrhythmias, myocardial ischemia, and heart failure; and for the development and performance optimization of medical devices, ultimately enabling manufacturers to predict device and procedure performance and outcome prior to clinical trials. Attempt is made to extend these models beyond electromechanics and include regulatory processes such as energy metabolism and signal transduction. Here we provides specific examples of the state-of-the-art in cardiac integrative modeling, including 1) uncovering the role of ventricular structure in defibrillation; 2) improving ventricular ablation procedure by using MRI reconstructed heart geometry and structure to investigate the reentrant circuits formed in the presence of an infarct scar; 3) employing an electromechanical model of the heart to determine the electromechanical delay in the heart; and 4) understanding the origin of mechanically-induced ventricular premature beats in acute regional ischemia.