Abstract
Ventricular arrhythmias (VA) in patients with myocardial infarction (MI) are thought to
be associated with structural and electrophysiological remodeling within the infarct
border zone (BZ). Personalized computational models have been used to investigate
the potential role of the infarct BZ in arrhythmogenesis, which still remains incompletely
understood. Most recent models have relied on experimental data to assign BZ
properties. However, experimental measurements vary significantly resulting in different
computational representations of this region. Here, we review experimental data
available in the literature to determine the most prominent properties of the infarct BZ.
Computational models are then used to investigate the effect of different representations
of the BZ on activation and repolarization properties, which may be associated with
VA. Experimental data obtained from several animal species and patients with infarct
show that BZ properties vary significantly depending on disease’s stage, with the early
disease stage dominated by ionic remodeling and the chronic stage by structural
remodeling. In addition, our simulations show that ionic remodeling in the BZ leads to
large repolarization gradients in the vicinity of the scar, which may have a significant
impact on arrhythmia simulations, while structural remodeling plays a secondary role. We
conclude that it is imperative to faithfully represent the properties of regions of infarction
within computational models specific to the disease stage under investigation in order to
conduct in silico mechanistic investigations.
Keywords: cardiac electrophysiology, myocardial infarct, inf
be associated with structural and electrophysiological remodeling within the infarct
border zone (BZ). Personalized computational models have been used to investigate
the potential role of the infarct BZ in arrhythmogenesis, which still remains incompletely
understood. Most recent models have relied on experimental data to assign BZ
properties. However, experimental measurements vary significantly resulting in different
computational representations of this region. Here, we review experimental data
available in the literature to determine the most prominent properties of the infarct BZ.
Computational models are then used to investigate the effect of different representations
of the BZ on activation and repolarization properties, which may be associated with
VA. Experimental data obtained from several animal species and patients with infarct
show that BZ properties vary significantly depending on disease’s stage, with the early
disease stage dominated by ionic remodeling and the chronic stage by structural
remodeling. In addition, our simulations show that ionic remodeling in the BZ leads to
large repolarization gradients in the vicinity of the scar, which may have a significant
impact on arrhythmia simulations, while structural remodeling plays a secondary role. We
conclude that it is imperative to faithfully represent the properties of regions of infarction
within computational models specific to the disease stage under investigation in order to
conduct in silico mechanistic investigations.
Keywords: cardiac electrophysiology, myocardial infarct, inf
| Original language | English |
|---|---|
| Article number | 356 |
| Journal | Frontiers in Physiology |
| Volume | 9 |
| Early online date | 9 Apr 2018 |
| DOIs | |
| Publication status | Published - Apr 2018 |