# Bioelectric monitoring and neuromodulation of the heart

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2024 · $822,301

## Abstract

ABSTRACT:
 The incidence of cardiac arrest in the United States exceeds 300,000 per year with an average survival rate
of ~11%. Over 500,000 cardiac surgeries and procedures, which require detailed cardiac diagnostics and
intense monitoring, are performed to treat arrhythmias and structural heart disease in the US each year, which
together carry a morbidity and mortality risk of 1-30%, depending on a patient’s comorbidities. The
fundamental hypothesis underlying this proposal is: Progression of arrhythmogenesis reflects heterogeneities
in cardiac electrical substrate that are amplified by heterogeneities in autonomic control. As such,
interventions that mitigate autonomic heterogeneities should be (and are) anti-arrhythmic. A major unmet
need in the field of Neurocardiology is technologies that provide real-time predictive assessments of cardiac
and autonomic status that would then allow for rapid and targeted closed-loop neuromodulation therapies to
intervene in the progression of arrhythmogenesis. The primary goal of this proposal is to develop bioelectronic
technologies for high-resolution, real-time concurrent measurements of cardiac autonomic and
electrophysiological parameters and to use that information to modulate autonomic function in a feedback
control manner. Advances in analytics for data derived from intra-myocardial multi-pole electrodes, coupled
with the deployment of thin-film 2-D microarrays to the epicardium, will define electrical heterogeneities across
the border zone areas of the ischemic heart. Autonomic assessment will include real-time measurement of
regional cardiac neurotransmitter release profiles, leveraging electrochemical cyclic voltammetry
(catecholamine) and capacitive immunoprobe (neuropeptide measurements), each novel to the cardiac
setting. The ability to provide real-time readouts of vascular and cardiac neurochemicals, when combined
with our advances in direct epicardial and endocardial mapping of the cardiac electrical substrate, provides
our team the ability to 1) identify subjects at high risk for sudden cardiac death; 2) define specific contribution
of abnormal electrophysiological substrate as amplified by heterogeneities in autonomic neurotransmitters;
and 3) tailor closed-loop neuromodulation therapeutic interventions to the underlying pathology. To this end,
three aims are proposed. Aim 1: To develop bioelectronic interfaces, platforms/modules, and analytical tools
for real-time in vivo assessments of multiple cardiac interstitial and vascular neurotransmitter levels. Aim 2:
To define dynamic interactions between focal cardiac neurotransmitter release and modulation of regional
cardiac electrical function in reflex response to cardiac stress. Aim 3: To implement a Multi Input, Multi Output
(MIMO) closed-loop control of cardiac transmitters. The translational potential of such a closed-loop
neuromodulation system will find application in intraoperative, post-operative and critical care settings.

## Key facts

- **NIH application ID:** 10809693
- **Project number:** 5R01HL162921-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** KALYANAM SHIVKUMAR
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $822,301
- **Award type:** 5
- **Project period:** 2023-04-01 → 2027-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10809693

## Citation

> US National Institutes of Health, RePORTER application 10809693, Bioelectric monitoring and neuromodulation of the heart (5R01HL162921-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10809693. Licensed CC0.

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