Renewal Rate Constants of Phase Singularity Formation and Destruction in Atrial Fibrillation are Temporally Stable Measures of Fibrillatory Dynamics

Dhani Dharmaprani1, Jing Quah2, Andrew McGavigan2, Anand Ganesan2
1Flinders University, 2Flinders Medical Centre


Abstract

Background: The optimal approach for atrial fibrillation (AF) ablation is unknown, with a subset of patients unresponsive to current strategies. In such patients, development of novel mechanism-based approaches could be needed, but this requires a stable, robust and easily measurable marker of underlying AF dynamics. We hypothesized that renewal rate constants λf and λd, previously shown to quantify rates of phase singularity (PS) formation and destruction during fibrillation, could be used as such a marker.

Objective: We hypothesised λf/λd are temporally stable and can be used as robust markers of underlying fibrillatory dynamics.

Methods: Basket recordings from n=20 patients (43 epochs) and n= 12 sheep (20 epochs) were studied. Temporal stability of λf/λd was analyzed by investigating if averages created using 20 second windows (i) have a stable mean, ii) time-independent autocorrelation functions, and iii) if coefficient of variation (CV) of λf/λd over time are lower than for established measures (dominant frequency (DF) and AF cycle length (AFCL)).

Results: Mean λf/λd estimated from 20 second windows was constant (R2λf=0.97; R2λd=0.99), with time-invariant autocorrelation functions. CV was also lowest for λf (3.7% (95%CI,1.6,5.9)) and λd (2.6% (1.5,3.8)) compared to DF (16.3% (95%CI,2.5,30)) and AFCL (12.2% (95%CI,6.7,17.7)), and also significantly different to DF (P < 0.001) and AFCL (P < 0.001).

Conclusions: λf/λd are temporally stable, providing a robust and clinically usable mechanistic tool to directly quantify AF dynamics, mechanistically connected to rotor regeneration that is the key to underlying AF perpetuation.