Atrial Fibrillation Dynamics and Ionic Block Effects in Six Heterogeneous Human 3D Virtual Atria with Distinct Repolarization Dynamics

Figures

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  Figure 1. Considered atrial fibrillation (AF) phenotypes based on cellular repolarization characteristics. (A) Population of simulated AF cell models calibrated against experimental recordings (black). The baseline Maleckar et al. model after chronic-AF remodeling (magenta) is provided for comparison. (B–D) First (blue) and fourth (red) quartile subpopulations according to APD90, APD50, and APD20, respectively, together with the corresponding histograms. Note magnification in time axis in panel (D). (E) Scatter plots of experimentally measured APD90, APD50, and APD20. Dotted lines represent first and third quartile values for each group of experimental action potential durations (APDs). (F) Venn diagrams with the number of action potential (APs) belonging to one, two, or three subpopulations of models for different intersections of short and long APD phenotypes.

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  Figure 2. Median values and ranges of variability in ionic conductances in the six subpopulations of human atrial action potential models under atrial fibrillation remodeling. Blue and red indicates short and long APD90, APD50, and APD20, respectively. Each boxplot represents the range covered by the ionic conductances: the edges of the box are the first and third quartiles, whiskers extend to the most extreme data points, the estimated median physiological value is the central horizontal line and the notch around the median is the 5% significance level.

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  Figure 3. Modulation of atrial fibrillation reentrant dynamics by intersubject variability in action potential phenotype. Interpolated maps show dorsal views of the atria for dominant frequency (DF), organization index (OI), regularity index (RI), and coupling index (CP) between adjacent electrogram (thick white lines represent CP > 0.9, thin solid lines represent 0.75 ≤ CP < 0.9, and soft gray lines represent 0.6 ≤ CP < 0.75. CP < 0.6 is represented by absence of lines) for short and long APD90, APD50, and APD20 virtual phenotypes.

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  Figure 4. ContinuedModulation of dominant frequency (DF) of reentry in atrial fibrillation by intersubject variability in action potential phenotype in response to ion channel block. Interpolated DF maps (dorsal view of the atria) are shown for short and long APD90, APD50, and APD20 subpopulations of models before (default) and after 30% IK1 inhibition, 30% INaK inhibition, and 15% INa inhibition, respectively.

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  Figure 5. Modulation of organization index (OI) of reentry in atrial fibrillation by intersubject variability in action potential phenotype in response to ion channel block. Interpolated OI maps (dorsal view of the atria) are shown for short and long APD90, APD50, and APD20 subpopulations of models before (default) and after 30% IK1 inhibition, 30% INaK inhibition, and 15% INa inhibition, respectively.

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  Figure 6. Modulation of regularity index (RI) of reentry in atrial fibrillation by intersubject variability in action potential phenotype in response to ion channel block. Interpolated RI maps (dorsal view of the atria) are shown for short and long APD90, APD50, and APD20 subpopulations of models before (default) and after 30% IK1 inhibition, 30% INaK inhibition, and 15% INa inhibition, respectively.

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  Figure 7. Modulation of coupling index (CP) of reentry in atrial fibrillation by intersubject variability in action potential phenotype in response to ion channel block. Dorsal views of the left atrium (left) and right atrium (right) are shown. CP between electrogram in adjacent electrodes (thick white lines represent CP > 0.9, thin solid lines represent 0.75 ≤ CP < 0.9, and soft gray lines represent 0.6 ≤ CP < 0.75. CP < 0.6 is represented by absence of lines) for short and long APD90, APD50, and APD20 subpopulations of models before (default) and after 30% IK1 inhibition, 30% INaK inhibition, and 15% INa inhibition, respectively.

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  Figure 8. Modulation by action potential (AP) phenotype in intra-subject and intersubject variability in response to drug block. Percentages of variation of average indices of atrial fibrillation reentrant dynamics [dominant frequency (DF), organization index (OI), regularity index (RI), and coupling index (CP) x-axes] are presented for the six considered AP phenotypes. Top and bottom rows show results for left atrium (LA) and right atrium (RA), under partial block of IK1 (left column), INaK (middle column), and INa (right column), respectively.