ABSTRACT More than 450,000 hospitalizations each year in the US are due to atrial fibrillation (AF) which contributes to approximately 160,000 deaths. The incidence of stroke, morbidity, hospitalization and mortality is further exacerbated by the 40% of heart failure (HF) patients who suffer from AF. The intertwined pathology between AF and HF have emerged as global epidemics poised to dominate cardiovascular care for the next half-century, imposing a staggering $372 million annual increase to the US healthcare system, and amplifying the urgency for effective therapies. Catheter ablation has become an increasingly common treatment for AF despite limited and highly variable success rates and complications, with arrhythmia-free survival rates < 29% at 5 years. The current acute standard of care is external cardioversion, with or without antiarrhythmic drugs. Unfortunately, high-voltage external shocks are extremely painful, can cause additional arrhythmias, and often require escalation of care at an annual cost of ~$26 billion. Efforts to address this unmet need have focused on internal atrial cardioversion, which has not been widely adopted due to the invasiveness and patient intolerability of the pain from high-energy shocks. The Maxwell Biomedical Spatial Resynchronization Therapy (SRT) System resolves the limitations of high energy cardioversion for treating AF by utilizing spatiotemporal identification of the excitable gap and ultra- low energy stimulation within the gap to globally advance refractoriness of complex reentry patterns enabling imperceptible pace-termination of AF. This is accomplished via a multi-site pacing electrode array lead system (MPEALS), which consists of multiple paired electrodes that, when implanted, are distributed across the posterior-inferior epicardial region of the left atrium and tunneled to a subcutaneous pocket located under the left arm/shoulder and connected to a rechargeable pulse generator. The system records cardiac electrograms from each of the electrodes and the algorithm analyzes these signals to determine electronic selection and timing of stimulation at each electrode using a state-of-the-art method from Dynamical System Theory. Importantly, it operates below 0.1 J, an order of magnitude below the threshold for pain. Evidence for the effectiveness of this approach has been shown in bench simulations, in vivo swine, and first-in-human studies (n=10) where an external system (MAX-SRS) connected to commercially available multipolar catheters placed during open-heart surgery achieved 83.3% global synchrony across 48 independent test runs, demonstrating a remarkable ability to effectively terminate AF. The Maxwell Biomedical SRT system is now ready for final refinement of the algorithm (Aim 1) in parallel with development of the MPEALS (Aim 2) which will be evaluated for efficacy, safety and deliverability with an implantable pulse generator as a complete system to capture, gain control and terminate AF i...