Effects of electrical and structural remodeling on atrial fibrillation maintenance: a simulation study

Abstract

Atrial fibrillation, a common cardiac arrhythmia, often progresses unfavourably: in patients with long-term atrial fibrillation, fibrillatory episodes are typically of increased duration and frequency of occurrence relative to healthy controls. This is due to electrical, structural, and contractile remodeling processes. We investigated mechanisms of how electrical and structural remodeling contribute to perpetuation of simulated atrial fibrillation, using a mathematical model of the human atrial action potential incorporated into an anatomically realistic three-dimensional structural model of the human atria. Electrical and structural remodeling both shortened the atrial wavelength--electrical remodeling primarily through a decrease in action potential duration, while structural remodeling primarily slowed conduction. The decrease in wavelength correlates with an increase in the average duration of atrial fibrillation/flutter episodes. The dependence of reentry duration on wavelength was the same for electrical vs. structural remodeling. However, the dynamics during atrial reentry varied between electrical, structural, and combined electrical and structural remodeling in several ways, including: (i) with structural remodeling there were more occurrences of fragmented wavefronts and hence more filaments than during electrical remodeling; (ii) dominant waves anchored around different anatomical obstacles in electrical vs. structural remodeling; (iii) dominant waves were often not anchored in combined electrical and structural remodeling. We conclude that, in simulated atrial fibrillation, the wavelength dependence of reentry duration is similar for electrical and structural remodeling, despite major differences in overall dynamics, including maximal number of filaments, wave fragmentation, restitution properties, and whether dominant waves are anchored to anatomical obstacles or spiralling freely.

Figure 1. Reentrant activity in computer simulations of normal tissue (A) and tissue with full electrical plus structural remodeling (B).

Different views are obtained at the same point in time for each simulation and show left atrial free wall (upper left), left and right atria in a posterior view (upper right), tricuspid annulus and mitral annulus (lower left), and right atrial free wall (lower right). Abbreviations: left atrium (LA), right atrium (RA), left pulmonary veins (LPV), right pulmonary veins (RPV), superior vena cava (SVC), inferior vena cava (IVC), tricuspid annulus (TA), mitral annulus (MA). Reentry was initiated in the left atrial free wall in both cases. Snapshots were taken after 510 ms (A) and 9 s (B).

Figure 2. Remodeling increases reentry duration and maximal number of filaments.

Dependence of mean duration of reentrant activity (A) and maximal number of filaments (B) on the levels of electrical and structural remodeling.

Figure 3. Shortened wavelength increases reentry duration and maximal number of filaments.

Dependence of mean duration of reentrant activity (A) and maximal number of filaments (B) on the wavelength during electrical (black circles) or structural (gray squares) remodeling.

Figure 4. Primary and concomitant changes in APD and CV with remodelling.

Dependence of APD (A and B), CV (C and D), and WL (E and F) on the degree of electrical or structural remodeling.

Figure 5. Typical long-term patterns of reentry in computer simulations of atrial tissue with different combinations of remodeling.

Left and right columns in each of A, B and C, show two different views obtained at the same time points. Snapshots are 30 ms apart. Reentry anchored to the left pulmonary veins (LPV) during full electrical remodeling (A). Reentry around the tricuspid annulus (TA) and the inferior vena cava (IVC) during full structural remodeling (B). Un-anchored reentry in the left atrial free wall and anchored reentry around the superior vena cava (SVC) with full electrical plus structural remodeling (C).