# CARDIAC NEUROMODULATION IN HUMANS: MECHANISMS & THERAPIES

> **NIH NIH OT2** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2020 · $730,343

## Abstract

Current state of knowledge on the etiology and clinical characteristics of cardiovascular
disease: Cardiovascular disease is the leading cause of morbidity and mortality in the US and
the world. The autonomic nervous system (ANS) plays a central role in the pathogenesis of
several cardiovascular diseases such as atrial fibrillation, hypertension, myocardial infarction
(MI), ventricular tachyarrhythmias/fibrillation (VT/VF) and in the progression of heart failure
(HF). Heart failure also places a major financial burden on the US health system, affecting
five million people, and it is estimated to grow to eight million by 2030. Sympathovagal balance,
seen in normal health, is perturbed in the presence of cardiac disease leading to ‘net’
sympathoexcitation, which is due to an increase in sympathetic output and a concomitant
decrease in parasympathetic output. Neuromodulation therapies are directed toward restoring
sympathovagal balance and thereby attempt to reverse/prevent progression of cardiovascular
disease. Neuromodulation therapies such as stellate ganglionectomy/cardiac sympathetic
denervation (CSD) are now being clinically utilized and other neuraxial approaches show a
lot of promise including vagus nerve stimulation (VNS). However, clinical trials have
shown mixed results preventing broad application of therapy. This highlights the major
knowledge gap that exists regarding their mechanisms of action and the determination of
optimal bioelectric parameters and physiological readouts in the clinical setting. As an
example, tragal vagus nerve stimulation (TVNS), has demonstrated potential benefit in reducing
inflammation and preventing progressive myocardial pathological remodeling. However, little is
known about how to dose the therapy to maximize the effects of TVNS in preventing or
reversing autonomic dysfunction in patients who have already suffered from cardiac disease
such as MI. In a series of translational/mechanistic studies, neuromodulation will be applied to
healthy subjects and to those with heart disease (MI or VT) to define optimal parameters and
readouts and to determine how neuromodulation impacts electrophysiological parameters of the
heart.

## Key facts

- **NIH application ID:** 10190645
- **Project number:** 3OT2OD028201-01S1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** KALYANAM SHIVKUMAR
- **Activity code:** OT2 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $730,343
- **Award type:** 3
- **Project period:** 2019-07-23 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10190645

## Citation

> US National Institutes of Health, RePORTER application 10190645, CARDIAC NEUROMODULATION IN HUMANS: MECHANISMS & THERAPIES (3OT2OD028201-01S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10190645. Licensed CC0.

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