Electrophysiological Substrates of Atrial Fibrillation: A Frequency Domain Study of Intra-cardiac Electrograms

The mechanisms responsible for maintenance of AF remain poorly understood. This thesis examines the frequency domain characteristics of AF in order to gain further insights into this arrhythmia. Through a series of studies involving patients undergoing catheter ablation for atrial fibrillation, intra-cardiac electrograms of AF were collected and analysed using Fast Fourier Transform to derive frequency domain parameters of dominant frequency (DF) and organization index (OI). It was found that intravenous flecainide reduced DF of AF, but only an associated increase in OI was predictive of successful return to sinus rhythm. In another study of patients having catheter ablation for persistent AF, a higher OI post-ablation was found to be associated with medium-term freedom of AF, suggesting that OI may be a useful guide to determine the extent of radiofrequency ablation needed. The effects of vagal blockade with atropine were also studied and compared with that of catheter ablation using a stepwise strategy of isolating the pulmonary veins, linear ablation and complex fractionated electrogram ablation, without deliberately targeting ganglionated plexi. This showed that atropine reduced DF and increased OI of AF electrograms, while decreasing mean RR intervals, standard deviation of RR intervals and 5th percentile of RR intervals. The directional changes of all the above parameters mirrored that of catheter ablation, suggesting that vagal blockade and catheter ablation not deliberately aimed at autonomic tissue can have similar effects on the frequency spectrum of AF, probably mediated through modulation of the autonomic tone. The relationship of regional DF and electrogram complexity as assessed by automated measurement of complex fractionated electrogram – mean (CFE-mean) were also compared, pre and post-ablation of the left atrium. There appeared to be only a modest correlation between the two and this was further weakened following ablation, suggesting that these are possibly separate substrate entities.