Use of Atrial Fibrillation Electrograms and T1/T2 Magnetic Resonance Imaging to Define the Progressive Nature of Molecular and Structural Remodeling: A New Paradigm Underlying the Emergence of Persistent Atrial Fibrillation

Figure 1. Electrogram characteristics over rapid atrial pacing. A, High‐resolution mapping plaque. Electrogram measures CL (B), OI (C), and DF (D) dependent on pacing days in the posterior left atrium (N=31 for all parameters). CL indicates cycle length; DF, dominant frequency; and OI, organization index.

Figure 2. Decreasing bipolar voltage throughout the duration of RAP. A, Bipolar voltage decreased strongly over RAP days (R=0.6, P<0.05) in the PLA (N=31). Example voltage map after 50 days of RAP (B) compared with after 230 RAP days (C), and the corresponding histograms (D and E) show the decrease over increased RAP days. PLA indicates posterior left atrium; and RAP, rapid atrial pacing.

Figure 3. Increasing parasympathetic nerve activity over rapid atrial pacing. A, Schematic of parasympathetic nerve activity recorded in the SLGP. B, Increased parasympathetic nerve activity (summation nerve signal amplitude) with increasing RAP weeks (N=33). C, Examples of parasympathetic nerve activity recordings over RAP weeks. AF indicates atrial fibrillation; ECG, electrogram; PNA, parasympathetic nerve activity; RAP, rapid atrial pacing; and SLGP, superior left ganglionic plexi.

Figure 4. Left atrial T1, T2, and ECV values over rapid atrial pacing. A, Average of 3‐chamber and short axes of T1 times increases with increasing RAP days in the PLA (N=25). B, Average of 3‐chamber and short axes of T2 times (N=25) increased with RAP days. C, No change in ECV over RAP days (average of 3‐chamber and short axes of atrial ECV) (N=25). D through F, Examples of T1 measurements over RAP time. Blue indicates ventricular tissue; orange, ventricular blood; purple, atrial tissue in the PLA in the upper figure panels (grayscale). Middle figure panels in D through F show a zoomed area (yellow) in color scale. Lower figure panels in D through F show atrial tissue selection of the PLA (marked in white) in the zoomed area. ECV indicates extracellular volume fraction; PLA, posterior left atrium; and RAP, rapid atrial pacing.

Figure 5. Oxidative stress and fibrosis over RAP days. A, Example of tissue with damaged nuclei after RAP. 8‐OHdG staining: oxidative stress‐damaged nuclei are stained in brown (red arrow), and undamaged nuclei in blue (blue arrow). B, Example of tissue with dense damaged nuclei in fat. C, Oxidative stress (%) (N=15) increased over RAP days in the left atrial regions (R=0.5, P<0.05). D, Fibrosis increased over RAP days (N=23) in the atrial regions PLA, LAFW, PRA, and RAFW (R=0.5, P<0.05). E, Fibrosis (%) increased with increasing oxidative stress levels (%) (R=0.6, P<0.05) (N=21). 8‐OHdG indicates 8‐hydroxy‐2′‐deoxyguanosine; LAFW, left atrial free wall; OS, oxidative stress; PLA, posterior left atrium; PRA, posterior right atrium; RAFW, right atrial free wall; and RAP rapid atrial pacing.

Figure 6. Summary figure. Earlier stage AF progression linked to OS and electrical remodeling can be measured in real time using electrograms (CL, OI, DF, and electrogram voltage) and nerve recordings (peaking at 80 RAP days). Longer‐term remodeling (after 80 RAP days) linked to fibrosis can be identified using the bipolar peak‐to‐peak electrogram voltage. MRI imaging including T1/T2 mapping may be complementary to detecting AF remodeling states. AF indicates atrial fibrillation; CL, cycle length; DF, dominant frequency; MRI, magnetic resonance imaging; OI, organization index; PLA, posterior left atrium; PNA, parasympathetic nerve activity; RAP, rapid atrial pacing; SLGP, superior left ganglionic plexi; and V, bipolar voltage.