Introduction: Renal dysfunction often develops in patients with heart failure with low ejection fraction due to hemodynamic and neurohumoral dysfunction leading to increased risk for mortality. Methods: The multi-center, prospective, open label Renal Denervation in Patients With Chronic Heart Failure & Renal Impairment (SYMPLICITY HF) trial enrolled NYHA Class II-III patients with left ventricular ejection fraction (LVEF) <40% and estimated glomerular filtration rate (eGFR) 30 to 75 mL/min/1.73m 2 . Subjects with systolic blood pressure < 90 mm Hg were excluded. The primary objective was to evaluate both the safety and physiologic response of renal denervation therapy on cardiac and renal function with the Symplicity™ renal denervation system using the Symplicity Flex™ catheter (Medtronic, Inc). Results: A total of 39 patients were enrolled (Table). No vascular complications occurred during the procedure. Available at AHA 2015 will be outcomes to 12 months follow up, including safety, cardiac function by echocardiography, and renal function by eGFR. Additionally, 9 subjects participated in a sub study that evaluated cardiac and renal noradrenaline spillover, muscle sympathetic nerve activity, and electrophysiological parameters by Holter monitor. Conclusions: Twelve-month outcomes in SYMPLICITY HF will provide initial insights into the safety and cardiac and renal physiologic impact of renal denervation in patients with heart failure.