Organization of ventricular fibrillation in the human heart: experiments and models

Abstract

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.

Electromechanical wavebreak in a model of the human left ventricle

“…Sudden cardiac death caused by cardiac arrhythmias is the most common cause of death in the industrialized world, and, in most cases, this is due to ventricular fibrillation (VF) (73). It has been shown in clinical and experimental studies (11,17,26,41,46,62,68,70) that VF occurs as a result of the onset of turbulent electrical activation patterns of the heart that are underpinned by multiple reentrant sources of excitation. Mechanisms behind the onset of reentrant sources in the heart and processes resulting in breakup of these sources into complex turbulent activation patterns are of great interest, e.g., in the design of therapeutic strategies to prevent or treat cardiac arrhythmias.…”

Bridging experiments, models and simulations: an integrative approach to validation in computational cardiac electrophysiology

“…As illustrated in Fig. 2, the representation of the anatomy of the upper or lower chambers of the heart (whole atria or whole ventricles models) is obtained from imaging modalities such as MRI and histology using segmentation techniques to obtain a binary image that defines the boundaries of the cardiac tissue (11,75,76,97,102,111). The binary image is then used to generate a volumetric mesh by applying a discretization process in space necessary to conduct the simulations, as described in the next section.…”

“…With respect to whole organ models, the process of iteration between experiments and simulations has been crucial, for example, to improving the understanding of important human health phenomena such as the dynamics of ventricular fibrillation (15,24,97), the most dangerous type of lethal arrhythmia, and the success and failure of electrical defibrillation, the only effective therapy against sudden cardiac death (98). In both cases, whole ventricular electrophysiology simulations were successfully combined with clinical and experimental methods to bring two important advantages.…”

“…First, the high spatiotemporal resolution data on the three-dimensional electrophysiological activity of the ventricles obtained from the simulations overcome limitations of clinical or experimental recordings, which are often restricted to low spatiotemporal resolution and/or just the surface of the heart. Second, computer models and simulations provide the ability to dissect the relative importance of different factors, which result in the identification of key properties such as the minimal action potential duration for ventricular fibrillation (96,97) or ventricular anatomy and structure for defibrillation (81,98). These novel findings could point toward new avenues for the preven- tion of ventricular fibrillation, both pharmacologically and electrically.…”

A novel, minimally invasive, segmental myocardial infarction with a clear healed infarct borderzone in rabbits

“…The rabbit heart shares with the human heart ion currents responsible for depolarization and repolarization, demonstrates an AP shape similar to that of the human, and has been successfully used in transgenic models (3,42). Furthermore, the rabbit heart appears to most resemble the human heart with respect to wave dynamics during complex arrhythmia such as ventricular fibrillation (46,64). Complex wave dynamics of ventricular fibrillation are most suitably investigated with high resolution optical mapping techniques using charged-coupled device cameras or photodiode arrays (9 -11, 34, 44, 56).…”