Neuromodulation of Inflammation and Endothelial Function

Heart failure with reduced ejection fraction (HFrEF) is a major cause of mortality in United States. Aging is a major risk factor for adverse outcomes associated with HFrEF, with majority of the patient's over the age of 50, continuing to experience symptoms, reduced exercise capacity and poor quality of life. We have previously demonstrated that low level transcutaneous electrical stimulation of the vagus nerve at the tragus (LLTS) suppresses inflammation in patients with atrial fibrillation and diastolic dysfunction and improved endothelial dysfunction in patients with chronic heart failure. The overall objective of this proposal is to examine the effects of LLTS on heart failure symptoms, exercise capacity and quality of life in patients with HFrEF and simultaneously determine the impact of LLTS on the suppression of inflammation and improvement in endothelial function. Our specific aims include: 1. To examine the medium term effect of intermittent (1 hour daily for 3 months) LLTS on exercise capacity and quality of life, related to sham stimulation, in patients with HFrEF, 2. To determine the effects of medium-term LLTS on sympathovagal/autonomic balance (assessed by heart rate variability) and systemic inflammation in patients with HFrEF and 3. To determine the effects of medium-term LLTS on endothelial function in patients with HFrEF. The proposed proof-of-concept human studies will provide the basis for the design of further human studies using LLTS among larger populations with HFrEF. In light of the increasing number of elderly patients who continue to experience HFrEF symptoms, recognized is a key point of interest in this funding mechanism, and the suboptimal success of the currently available treatment options to ameliorate the problems mentioned above, an alternative novel approach such as LLTS has the potential to impact clinical practice and improve health outcomes among the large number of patients. It is anticipated that these investigations will co