Abstract-Sudden cardiac death is a major cause of death in the industrialized world, claiming approximately 300 000 victims annually in the United States alone. In most cases, sudden cardiac death is caused by ventricular fibrillation (VF). Experimental studies in large animal hearts have shown that the uncoordinated contractions during VF are caused by large numbers of chaotically wandering reentrant waves of electrical activity. However, recent clinical data on VF in the human heart seem to suggest that human VF may have a markedly different organization. Here, we use a detailed model of the human ventricles, including a detailed description of cell electrophysiology, ventricular anatomy, and fiber direction anisotropy, to study the organization of human VF. We show that characteristics of our simulated VF are qualitatively similar to the clinical data. Furthermore, we find that human VF is driven by only approximately 10 reentrant sources and thus is much more organized than VF in animal hearts of comparable size, where VF is driven by approximately 50 sources. We investigate the influence of anisotropy ratio, tissue excitability, and restitution properties on the number of reentrant sources driving VF. We find that the number of rotors depends strongest on minimum action potential duration, a property that differs significantly between human and large animal hearts. Based on these findings, we suggest that the simpler spatial organization of human VF relative to VF in large animal hearts may be caused by differences in minimum action potential duration. Both the simpler spatial organization of human VF and its suggested cause may have important implications for treating and preventing this dangerous arrhythmia in humans. (Circ Res. 2007;100:e87-e101.)Key Words: ventricular fibrillation Ⅲ computer simulation Ⅲ spatial organization V entricular fibrillation (VF) is the single most common cause of sudden cardiac death, the largest cause of death in the Western world. During VF, the contraction of the ventricles becomes rapid, uncoordinated, and highly ineffective, causing this condition to be lethal within minutes, unless halted by defibrillation. The highly disorganized contractions during VF are caused by a severely disturbed, turbulent conduction of the electrical excitation wave.Experimental studies in animal hearts and tissue 1-6 have shown that the turbulent electrical activity typical of VF is caused by the presence of multiple reentrant waves of electrical excitation. Because of their reentrant behavior and high frequency, these rotors act as self-perpetuating, independent sources of excitation that take over control from the slower sinus node. The number of rotors present during VF is a good quantifier of the complexity and amount of disorganization of the excitation pattern. Results in animal hearts suggest that the number of reentrant sources present during VF increases as a function of heart size. For example, in rabbit hearts, VF can be driven by just 1 or 2 sources, 2,7 whereas in sheep hearts, VF...

Sudden cardiac death is a major health problem in the industrialized world. The lethal event is typically ventricular fibrillation (VF), during which the co-ordinated regular contraction of the heart is overthrown by a state of mechanical and electrical anarchy. Understanding the excitation patterns that sustain VF is important in order to identify potential therapeutic targets. In this paper, we studied the organization of human VF by combining clinical recordings of electrical excitation patterns on the epicardial surface during in vivo human VF with simulations of VF in an anatomically and electrophysiologically detailed computational model of the human ventricles. We find both in the computational studies and in the clinical recordings that epicardial surface excitation patterns during VF contain around six rotors. Based on results from the simulated three-dimensional excitation patterns during VF, which show that the total number of electrical sources is 1.4 ± 0.12 times greater than the number of epicardial rotors, we estimate that the total number of sources present during clinically recorded VF is 9.0 ± 2.6. This number is approximately fivefold fewer compared with that observed during VF in dog and pig hearts, which are of comparable size to human hearts. We explain this difference by considering differences in action potential duration dynamics across these species. The simpler spatial organization of human VF has important implications for treatment and prevention of this dangerous arrhythmia. Moreover, our findings underline the need for integrated research, in which humanbased clinical and computational studies complement animal research.