This paper reviews the newest developments in computational cardiology. It focuses on the contribution of cardiac modeling to the development of new therapies as well as the advancement of existing ones for cardiac arrhythmias and pump dysfunction. Reviewed are cardiac modeling efforts aimed at advancing and optimizing existent therapies for cardiac disease (defibrillation, ablation of ventricular tachycardia, and cardiac resynchronization therapy) and at suggesting novel treatments, including novel molecular targets, as well as efforts to use cardiac models in stratification of patients likely to benefit from a given therapy, and the use of models in diagnostic procedures. 1. Introduction The iterative interaction between experimentation and simulation has long played a central role in the advancement of biological sciences. Among computational models of the various physiological systems, the heart is the most highly advanced example of a virtual organ, capable of integrating data at multiple scales, from genes to the whole organ [1]. State-of-the-art whole-heart models of electrophysiology and electromechanics are currently being used to study a wide range of mechanisms in the workings of the normal and the diseased heart [2, 3]. The focus of this paper is on the contribution of heart computational models to the treatment of the diseased heart, that is, on the computational medicine aspect of cardiac modeling applications. Reviewed below are cardiac modeling efforts aimed at advancing and optimizing existent therapies for cardiac disease and at suggesting novel treatments, including novel molecular targets, as well as efforts to use cardiac models in stratification of patients likely to benefit from a given therapy, and the use of models in diagnostic procedures 2. Modeling Ventricular Arrhythmias: From Mechanisms to the Clinic Modeling arrhythmias in the whole heart to reveal mechanisms and suggest better treatments has become one of the most important hallmarks in the utilization of biophysically detailed computational modeling of the heart. A number of ventricular models have focused on arrhythmia dynamics, and specifically on the self-sustained reentrant propagation of complex 3D waves in the ventricles. Historically, these were the first applications of ventricular modeling. Ventricular modeling studies have revealed important aspects of reentrant arrhythmias, among which the dynamic characteristics of ventricular fibrillation (VF), and the role of alternans and restitution in arrhythmogenesis. Ventricular models have been used extensively in
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