Project Summary Atrial Fibrillation (AF) is the most common sustained arrhythmia in adults, carries a lifetime risk of 25-33%, and cost the US healthcare system > 6 Billion dollars a year. Morbidities from AF include congestive heart failure, dementia, symptoms due to decreased cardiac output, and most importantly an elevated thrombotic stroke risk due to blood stasis. Recent advances in wearable technology have increased the capacity and accuracy of AF diagnosis through monitoring heart rate variability in an ambulatory setting. However, there remains no available ambulatory technologies that permit continuous assessment of the hemodynamic effects of AF nor measurements of cardiac repolarization that determine the proarrhythmic effects of antiarrhythmic drugs. Some treatment aspects of AF have remained controversial due to limited efficacy of rhythm control interventions including cardiac ablation and pharmacologic therapy, both of which have significant risks. Pharmacologic interventions using Class III antiarrhythmics are especially risky due to the proarrhythmic effects on ventricular repolarization which can lead to life-threatening ventricular tachyarrhythmias such as torsades de pointes. As a result of these issues, careful assessment of ventricular repolarization, as represented by the QT interval on the electrocardiogram (ECG), is required during drug initiation. This requires lengthy and costly inpatient monitoring during drug loading and difficulties in maintaining the narrow therapeutic window after discharge. Having a reliable method to quantify measures of hemodynamic instability that leads to some AF- related symptoms, as well as continuously monitoring the QT interval and other clinically important parameters in an ambulatory setting would allow clinicians to tailor their care to the individual. This proposal aims to refine a flexible, non-obtrusive wearable system to continuously monitor these key clinical parameters, help in predicting heart rhythm complications and regulate medication intervention for both rhythm control and rate control of AF. A sensor suite consisting of a small, wireless and flexible chest-worn patch that measures both ECG and accelerometer based seismocardiography (SCG) and a wirelessly time synchronized flexible limb unit capable of monitoring photoplethysmographic (PPG) signals will be used. Aim 1 will quantitatively define the optimal location for QT interval monitoring on the surface of the chest. Aim 2 will combine the ECG, SCG, and PPG data streams and extract both unique and time-relational parameters from the signal streams known to be related to cardiac function and hemodynamics, using machine learning to obtain predictions of hemodynamic instability from these complex relationships. Aim 3 will address the use and compliance of this wearable system in a clinical setting against the standard of care during Class III antiarrhythmic drug loading and pharmacologic cardioversion. The results from this ...