Novel approaches for quantitative electrogram analysis for rotor identification: Implications for ablation in patients with atrial fibrillation

University of Minnesota Ph.D. dissertation. May 2017. Major: Biomedical Engineering. Advisor: Elena Tolkacheva. 1 computer file (PDF); xxviii, 349 pages + 4 audio/video filesAtrial fibrillation (AF) is the most common sustained cardiac arrhythmia that causes stroke affecting more than 2.3 million people in the US. Catheter ablation with pulmonary vein isolation (PVI) to terminate AF is successful for paroxysmal AF but suffers limitations with persistent AF patients as current mapping methods cannot identify AF active substrates outside of PVI region. Recent evidences in the mechanistic understating of AF pathophysiology suggest that ectopic activity, localized re-entrant circuit with fibrillatory propagation and multiple circuit re-entries may all be involved in human AF. Accordingly, the hypothesis that rotor is an underlying AF mechanism is compatible with both the presence of focal discharges and multiple wavelets. Rotors are stable electrical sources which have characteristic spiral waves like appearance with a pivot point surrounded by peripheral region. Targeted ablation at the rotor pivot points in several animal studies have demonstrated efficacy in terminating AF. The objective of this dissertation was to develop robust spatiotemporal mapping techniques that can fully capture the intrinsic dynamics of the non-stationary time series intracardiac electrogram signal to accurately identify the rotor pivot zones that may cause and maintain AF. In this thesis, four time domain approaches namely multiscale entropy (MSE) recurrence period density entropy (RPDE), kurtosis and intrinsic mode function (IMF) complexity index and one frequency domain approach namely multiscale frequency (MSF) was proposed and developed for accurate identification of rotor pivot points. The novel approaches were validated using optical mapping data with induced ventricular arrhythmia in ex-vivo isolated rabbit heart with single, double and meandering rotors (including numerically simulated data). The results demonstrated the efficacy of the novel approaches in accurate identification of rotor pivot point. The chaotic nature of rotor pivot point resulted in higher complexity measured by MSE, RPDE, kurtosis, IMF and MSF compared to the stable rotor periphery that enabled its accurate identification. Additionally, the feasibility of using conventional catheter mapping system to generate patient specific 3D maps for intraprocedural guidance for catheter ablation using these novel approaches was demonstrated with 1055 intracardiac electrograms obtained from both atria’s in a persistent AF patient. Notably, the 3D maps did not provide any clinically significant information on rotor pivot point identification or the presence of rotors themselves. Validation of these novel approaches is required in large datasets with paroxysmal and persistent AF patients to evaluate their clinical utility in rotor identification as potential targets for AF ablation