Novel entropy based identification of rotors in human atrial fibrillation Abstract Atrial Fibrillation (AF) or irregular chaotic electrical activation of the atria is the most common cardiac arrhythmia and is the leading source of health care expenditure in the United States. For the past years, there has been a rise in popularity of catheter ablation, which is an invasive non- pharmacological therapy that aims to restore normal sinus rhythm in the atria by eliminating triggers that initiate AF or by altering the substrate that maintains AF. Although more successful, recurrence rates are high, particularly in patients with persistent or long-standing AF. In these patients, AF is mostly maintained by the rotors that are located outside of pulmonary veins (PV) region. However, none of the currently available commercial mapping systems can predict the rotor location outside of PV in patients with persistent AF. Our preliminary data demonstrate that a novel entropy-based analysis can be used to identify pivotal points of rotors in animal hearts. These preliminary data were obtained using high-resolution optical mapping experiments in which direct visualization and identification of rotor location in the heart can be performed. In this proposal, we aim to confirm that the new technique, which is based on entropy estimation, can be used to identify pivotal (self-sustaining) regions of arrhythmias in humans with AF. We will enhance the analysis by providing a correlation between the new and already existing techniques at different atrial locations to reconstruct waveform propagation and to identify structural disruptions at sites of substrate abnormality. We propose to use already acquired database of clinical intracardiac electrograms from patients with paroxysmal, persistent, and long-standing AF who underwent electroanatomical mapping for AF ablation procedure.