The broad and long-term objective of this research project is to use, develop and market an instrument for the simultaneous recording of sympathetic nerve activity (SNA) and electrocardiogram (ECG) using electrodes on the skin. This method (neuECG) was discovered in Dr. Chen's research laboratory at the Krannert Institute of Cardiology, and a patent application has been filed by Indiana University. Arrhythmotech LLC was developed to further advance this concept and we propose that neuECG has a significant commercial value by providing a new non-invasive tool for arrhythmia prediction and detection. Sympathetic tone is important in cardiac arrhythmogenesis. Heart rate variability analyses and microneurography recordings are standard techniques to assess sympathetic tone. However, these techniques have multiple limitations. The neuECG was developed to record ECG and nerve activity simultaneously on the skin of human subjects. In collaboration with Dr. Chen's lab, we have obtained strong preliminary results in human patients to document the successful recording of neuECG in normal volunteers and in patients with postoperative atrial fibrillation and electrical storm. In these preliminary studies, neuECG recording showed electrical signals consistent with SNA, and that the SNA correlated with heart rate acceleration, atrial fibrillation and ventricular arrhythmias. We propose that the neuECG may serve as a new diagnostic tool for the prediction of cardiac arrhythmias and sudden cardiac death. In addition, it may be helpful in the diagnosis of diseases involving the peripheral nervous system, such as neuromuscular diseases. In this Phase 1 application, we have designed two clinical studies to document the feasibility and utility of neuECG recording in normal volunteers and in patients with cardiac arrhythmias. Once this is complete, we will immediately apply for Phase 2 funding to commercialize the neuECG for human use.
Specific Aim 1 : To record simultaneous ECG and SNA in normal volunteers and correlate the nerve activity to heart rate. We will consent normal volunteers for this study. We will place ECG electrodes on the skin using standard limb lead and chest lead configurations. The signals are digitized and filtered to record ECG and SNA simultaneously. After baseline recordings, the patients will undergo 2-min cold water immersion test, followed by Valsalva maneuver. The data will be analyzed to test the hypothesis that it is feasible to simultaneously record SNA from the skin, and that SNA recordings correlate with heart rate acceleration in normal volunteers.
Specific Aim 2 : To record simultaneous ECG and SNA in patients with cardiac arrhythmias and correlate an increase in nerve activity to arrhythmia onset. We will perform continuous neuECG recording at the bedside in patients with recurrent cardiac arrhythmias. The data will be analyzed to determine if the SNA are present on the skin of the diseased patients, and if the SNA correlates with the onset of cardiac arrhythmias. The results will be used to test the hypothesis that a continuous neuECG recording is feasible in patients with heart diseases, and that SNA predicts the impending onset of cardiac arrhythmias.

Public Health Relevance

Sympathetic nerve activity has been shown to be important in cardiac arrhythmogenesis and sudden cardiac death. The specific aims associated with this proposal are designed to simultaneously record sympathetic nerve activity and an electrocardiogram, then to correlate nerve activity to the onset of arrhythmias. This project will lead to the development of a new non-invasive and commercially viable method for assessing sympathetic tone and to improve arrhythmia risk stratification.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Small Business Technology Transfer (STTR) Grants - Phase I (R41)
Project #
1R41HL124741-01
Application #
8779946
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Krull, Holly
Project Start
2014-09-01
Project End
2015-02-28
Budget Start
2014-09-01
Budget End
2015-02-28
Support Year
1
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Arrhythmotech, LLC
Department
Type
DUNS #
City
Indianapolis
State
IN
Country
United States
Zip Code
46202
Jiang, Zhaolei; Zhao, Ye; Tsai, Wei-Chung et al. (2018) Effects of Vagal Nerve Stimulation on Ganglionated Plexi Nerve Activity and Ventricular Rate in Ambulatory Dogs With Persistent Atrial Fibrillation. JACC Clin Electrophysiol 4:1106-1114
Yin, Dechun; Chen, Mu; Yang, Na et al. (2018) Role of apamin-sensitive small conductance calcium-activated potassium currents in long-term cardiac memory in rabbits. Heart Rhythm 15:761-769
Shelton, Richard S; Ogawa, Masahiro; Lin, Hongbo et al. (2018) Effects of Stellate Ganglion Cryoablation on Subcutaneous Nerve Activity and Atrial Tachyarrhythmias in a Canine Model of Pacing-Induced Heart Failure. JACC Clin Electrophysiol 4:686-695
Everett 4th, Thomas H; Doytchinova, Anisiia; Cha, Yong-Mei et al. (2017) Recording sympathetic nerve activity from the skin. Trends Cardiovasc Med 27:463-472
Doytchinova, Anisiia; Hassel, Jonathan L; Yuan, Yuan et al. (2017) Simultaneous noninvasive recording of skin sympathetic nerve activity and electrocardiogram. Heart Rhythm 14:25-33
Uradu, Andrea; Wan, Juyi; Doytchinova, Anisiia et al. (2017) Skin sympathetic nerve activity precedes the onset and termination of paroxysmal atrial tachycardia and fibrillation. Heart Rhythm 14:964-971
Yin, Dechun; Hsieh, Yu-Cheng; Tsai, Wei-Chung et al. (2017) Role of Apamin-Sensitive Calcium-Activated Small-Conductance Potassium Currents on the Mechanisms of Ventricular Fibrillation in Pacing-Induced Failing Rabbit Hearts. Circ Arrhythm Electrophysiol 10:e004434
Tsai, Wei-Chung; Chan, Yi-Hsin; Hsueh, Chia-Hsiang et al. (2016) Small conductance calcium-activated potassium current and the mechanism of atrial arrhythmia in mice with dysfunctional melanocyte-like cells. Heart Rhythm 13:1527-35
Chinda, Kroekkiat; Tsai, Wei-Chung; Chan, Yi-Hsin et al. (2016) Intermittent left cervical vagal nerve stimulation damages the stellate ganglia and reduces the ventricular rate during sustained atrial fibrillation in ambulatory dogs. Heart Rhythm 13:771-80
Zhao, Ye; Jiang, Zhaolei; Tsai, Wei-Chung et al. (2016) Ganglionated plexi and ligament of Marshall ablation reduces atrial vulnerability and causes stellate ganglion remodeling in ambulatory dogs. Heart Rhythm 13:2083-90

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