Variability in pulmonary vein electrophysiology and fibrosis determines arrhythmia susceptibility and dynamics

Figures

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  Fig 1. Methods schematic. Schematic showing PV properties varied in this study: APD and conductivity were varied according to a normalized distance parameter indicated by colour; fiber direction (epicardial fibers in blue, endocardial fibers in red); geometry (colours indicate different atrial regions); and, fibrosis (dark blue indicates interstitial fibrosis). Asterisks indicate the pacing locations used for the inducibility pacing protocols.

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  Fig 2. Phase singularity trajectories depend on both PV properties and fibrosis distribution. Trajectories over time for control PV properties (CV: 0.67m/s, APD: 181ms; first two columns, anteroposterior and posteroanterior views); PVs with slow CV (CV: 0.51m/s; middle column); and PVs with short APD and slow CV (CV: 0.51m/s, APD: 120ms; right column). Rows indicate degree of fibrosis, with no fibrosis (control, top row); a distribution averaged over paroxysmal patients (middle row); a distribution averaged over persistent patients (bottom row). Colours indicate the time at which a PS was detected at a site.

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  Fig 3. Reentry anchors close to the LA/PV junction in cases with PV fibrosis. The leftmost column shows the normalized phase singularity density map as computed over 10 seconds. The three rightmost columns show snapshots of the transmembrane voltage at three time points. (A) For moderate PV fibrosis, the reentry location changes from the right veins to the left veins, resulting in areas of high PS density close to both sets of veins. (B) For high PV fibrosis, reentry occurs around both of the right PVs. Isopotential maps are at 50ms intervals, with different start times indicted by T1, T2 and T3. Reentry paths are indicated by circular arrows.

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  Fig 4. The relative importance of PV properties and atrial fibrosis in determining arrhythmia dynamics varies between patients. Top rows: clinical fibrosis and PS density mapped on to common atria for two patients, shown in posteroanterior and anteroposterior views. Bottom rows: Model PS density maps for low or high levels of fibrosis, and control or short PV APD or slow PV CV. PS densities are displayed in either posteroanterior or anteroposterior view depending on the location of areas of high PS density (LA2 with high fibrosis and short APD was non-sustained).

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  Fig 5. Arrhythmia inducibility and PS density varies between geometries and depends on PV area. (A) Inducibility against PV area for the LSPV (blue), LIPV (green), RIPV (red), RSPV (purple). (B) PV PS density ratio depends on total PV area. (C) Normalised PS density maps for 12 geometries.

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  Fig 6. PV PS density ratio is higher for successful PVI cases. Simulation outcomes after PVI were classified as termination (no activity), macroreentry (a large reentry circuit around the LA/PV junctions), or AF sustained by LA rotors (drivers in the LA body). Box plots show PV PS density ratio pre-PVI. Termination PV PS density ratio is significantly higher than for LA rotors (p<0.001), and macroreentry PV PS density ratio is significantly higher than for LA rotors (p = 0.01).