# Neuromodulation of inflammation and endothelial function to treat elderly patients with systolic heart failure.

> **NIH NIH R21** · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · 2022 · $179,000

## Abstract

Heart failure with reduced ejection fraction (HFrEF) is a major cause of morbidity and mortality in
United States. Aging and HFrEF are unique in that they share common pathologies, such as
autonomic imbalance (increased sympathetic and reduced parasympathetic tone), inflammation
(termed “inflammaging”) and endothelial dysfunction. Aging is a major risk factor for adverse
outcomes associated with HFrEF. Despite treatment, majority of HFrEF patients continue to
experience reduced exercise capacity and poor quality of life (QoL). Recent studies have
suggested that age-associated autonomic imbalance, inflammation and endothelial dysfunction
may play a central role in the progression of HFrEF, supporting the notion that attenuating these
abnormalities may help improve clinical outcomes in HFrEF. We have previously demonstrated
that low level transcutaneous tragus stimulation (LLTS) improves autonomic imbalance and
suppresses inflammation in patients with atrial fibrillation and diastolic dysfunction and improved
endothelial dysfunction in patients with HFrEF. The overall objective of this proposal is to
examine the effects of LLTS on exercise capacity and QoL in patients with HFrEF and
simultaneously determine its impact on the core age-related pathologic axes, autonomic
imbalance, inflammation and endothelial dysfunction. Our specific aims include: 1. To examine
the medium-term effect of intermittent (1-hour daily for 3 months) LLTS on exercise capacity and
QoL, relative to sham stimulation, in patients with HFrEF, 2. To determine the effects of medium-
term LLTS on autonomic imbalance (assessed by heart rate variability) and 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 feasibility study will provide
the basis for using LLTS among larger HFrEF populations. This proposal intends to a) elucidate
the effects of LLTS on age-related abnormalities (autonomic imbalance, inflammation and
endothelial dysfunction) and progression of HFrEF outcomes (exercise capacity and QoL) and b)
develop and further refine novel therapies, such as LLTS, to ameliorate the underlying age-
associated derangements and clinical outcomes. In light of the increasing number of elderly
patients who, despite treatment, continue to experience HFrEF symptoms, recognized is a key
point of interest in this funding mechanism, an alternative novel approach such as LLTS has the
potential to improve health outcomes in HFrEF. It is anticipated that these investigations will
contribute to a broader understanding of age-associated autonomic imbalance, inflammation and
endothelial dysfunction in HFrEF and how its inhibition can be used to provide therapeutic effects.

## Key facts

- **NIH application ID:** 10353835
- **Project number:** 1R21AG075639-01
- **Recipient organization:** UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR
- **Principal Investigator:** TARUN DASARI
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $179,000
- **Award type:** 1
- **Project period:** 2022-03-01 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10353835

## Citation

> US National Institutes of Health, RePORTER application 10353835, Neuromodulation of inflammation and endothelial function to treat elderly patients with systolic heart failure. (1R21AG075639-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10353835. Licensed CC0.

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