Heart failure with preserved ejection fraction (HFpEF) is a leading cause of mortality in the elderly. Outcomes of patients with HFpEF are poor and so far, no treatment has been shown to decrease morbidity or mortality. Recent animal and human studies suggest that a systemic proinflammatory state produced by comorbidities, including aging, plays a central role in the development of HFpEF, supporting the notion that attenuating the proinflammatory state is an attractive therapeutic target for HFpEF. We have previously shown that low-level transcutaneous electrical stimulation of the vagus nerve at the tragus (LLTS) suppresses inflammation in patients with atrial fibrillation. The overall objective of this proposal is to examine the effects of LLTS on diastolic dysfunction, exercise capacity and inflammation in patients with HFpEF and determine whether these effects are mediated by suppression of inflammation and fibrosis in a well-established rat model of HFpEF.
Our specific aims i nclude: 1. To examine the effect of intermittent (1 hour daily for 3 months) LLTS on diastolic dysfunction, exercise capacity and inflammation, relative to sham stimulation, in patients with HFpEF and 2. To determine the effect of intermittent (30 minutes daily for 4 weeks) LLTS on diastolic dysfunction, inflammation and fibrosis in a well-established HFpEF rat model. The proposed proof-of-concept human studies and mechanistic animal studies will provide the basis for the design of further human studies using LLTS among populations with HFpEF. In light of the increasing number of elderly patients with HFpEF, recognized as a key point of interest in this funding mechanism, and the poor success of the currently available treatment options, an alternative and novel approach such as LLTS has the potential to impact clinical practice and improve health outcomes among a large number of patients. It is anticipated that these investigations will contribute to the broader understanding of the role of inflammation in the pathogenesis of HFpEF and how its inhibition can be used to provide therapeutic effects. Moreover, it is anticipated that a better understanding of how modulation of inflammation affects one of the hallmarks of HFpEF, diastolic dysfunction, will lead to the development of novel pharmacological and non-pharmacological approaches to treat this disease.
Heart failure with preserved ejection fraction (HFpEF) is a type of heart failure characterized by stiffening of the heart muscle. It is very common condition, but there has not been a treatment for HFpEF that has been shown to decrease deaths or hospitalizations. Recent animal and human studies suggest that inflammation plays a central role in the development of HFpEF. Therefore, attenuating inflammation is an attractive target for the treatment of HFpEF. Stimulation of the vagus nerve has been shown to decrease inflammation in multiple animal and human studies. We have recently shown that vagus nerve stimulation can be accomplished non- invasively by attaching stimulating electrodes at the tragus of the ear and that tragus stimulation decreases inflammatory markers in humans. In this study, we aim 1) to examine the effects of daily (1 hour for 4 weeks) tragus stimulation on echocardiographic markers of diastolic dysfunction (stiffening of the heart muscle), exercise capacity, and inflammatory markers in the blood, in humans with HFpEF and 2) to examine the effects of daily, short-term (30 minutes for 4 weeks) tragus stimulation on inflammatory markers and echocardiographic markers of diastolic dysfunction in a rat model of HFpEF. The proposed proof-of-concept human studies and mechanistic animal studies will provide the basis for the design of further human studies using tragus stimulation among populations with HFpEF. In light of the increasing number of elderly patients with HFpEF, recognized as a key point of interest in this funding mechanism, and the poor success of the currently available treatment options, an alternative and novel approach such as tragus stimulation has the potential to impact clinical practice and improve health outcomes among a large number of patients.
| Tran, Nicole; Asad, Zain; Elkholey, Khaled et al. (2018) Autonomic Neuromodulation Acutely Ameliorates Left Ventricular Strain in Humans. J Cardiovasc Transl Res : |
