PROJECT SUMMARY Cardiac arrhythmias are a major cause of morbidity and mortality affecting over 5% of Americans. Arrhythmias have become increasingly prevalent due to an aging population with diabetes, heart failure and hypertension, which has led to an increasing number of invasive electrophysiology studies and catheter ablations. Our grasp of the cardiac arrhythmia mechanism, if it is focal or reentrant, and the specific location of the arrhythmia origin is limited by the current first-line, standard of care, noninvasive diagnostic test — the 12-lead electrocardiogram (ECG), which is dependent on physician subjective interpretation. Furthermore, it does not present the arrhythmia in an easily visualized, three-dimensional, anatomical manner for patients or physicians to understand. Other noninvasive mapping techniques such as ECG imaging (ECGI) or virtual-heart technology, requires additional preprocedural imaging such as computed tomography which exposes patient to radiation, or magnetic resonance imaging which is costly. Over ten years, the collaborative team effort between Cardiac Electrophysiology and Biomedical Engineering at Columbia University Irving Medical Center, has developed Electromechanical Wave Imaging (EWI), an ultrasound-based technique that takes 10-15 minute to non- invasively image arrhythmias by visualizing the electromechanical wave corresponding to electromechanical coupling. We have now developed a new technique, a full 3D EWI noninvasive ultrasound technique which can construct an entire 4 chamber cardiac activation map using a single heartbeat of arrhythmia acquired in one apical transthoracic echocardiographic image. We propose three aims which will validate non-invasive 3D EWI to high density activation maps (HDAM) acquired during invasive electrophysiology study and demonstrate its clinical impact to shorten procedural times and improve clinical outcomes in a randomized clinical trial. We will demonstrate that 3D EWI is an invaluable tool for pre-ablation planning to (1) provide target localization, (2) diagnose the mechanism of the arrhythmia, as focal or macro-reentrant arrhythmia, useful in decision-making for systemic anticoagulation and (3) improve ablation outcomes. We will study patients with manifest pre- excitation such as Wolff-Parkinson-White syndrome, atrial tachycardia, atrial flutter, premature atrial complexes, premature ventricular complexes and ventricular tachycardia at two clinical sites, Columbia University (NY, NY) and Mount Sinai Medical Center (NY, NY). This project presents a strong team with imaging expertise in ultrasonography, clinical cardiac electrophysiology and biostatistics. Using a collaborative, multi-disciplinary and integrated experimental approach we will clinically validate noninvasive 3D EWI with invasive 3D HDAM and deliver a translational and transformative technique with immediate clinical impact that will enable personalized imaging for ablation of cardiac arrhythmias.

Public Health Relevance Atrial and ventricular cardiac arrhythmias, are serious public health problems in the United States, affecting over 5% of Americans and are major causes of stroke and heart failure leading to increased morbidity and mortality. This proposed preclinical study and clinical trial will determine how electromechanical wave imaging, a non- invasive ultrasound precision imaging modality can effectively diagnose and determine the mechanism of the arrhythmia and impact personalized treatment of cardiac arrhythmias.