Author + information
- Received December 9, 2019
- Revision received February 6, 2020
- Accepted February 14, 2020
- Published online May 18, 2020.
- Stavros Stavrakis, MD, PhDa,∗ (, )
- Kanchan Kulkarni, PhDb,
- Jagmeet P. Singh, MD, PhDc,
- Demosthenes G. Katritsis, MD, PhDd and
- Antonis A. Armoundas, PhDb,e,∗∗ ()
- aHeart Rhythm Institute, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma
- bCardiovascular Research Center, Massachusetts General Hospital, Boston, Massachusetts
- cCardiology Division, Cardiac Arrhythmia Service, Massachusetts General Hospital, Boston, Massachusetts
- dHygeia Hospital, Athens, Greece
- eInstitute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, Massachusetts
- ↵∗Address for correspondence:
Dr. Stavros Stavrakis, Heart Rhythm Institute, University of Oklahoma Health Sciences Center, 800 Stanton L Young Boulevard, Suite 5400, Oklahoma City, Oklahoma 73104.
- ↵∗∗Dr. Antonis A. Armoundas, Cardiovascular Research Center, Massachusetts General Hospital, 149 13th Street, Charlestown, Massachusetts 02129.
• The autonomic nervous system plays a central role in the pathogenesis of multiple cardiac arrhythmias, including AF and ventricular tachycardia.
• Autonomic modulation therapeutic modalities (such as VNS, tragus stimulation, RDN, BAT, and CSD) have shown promise in early preclinical studies and clinical trials as alternatives to standard arrhythmia treatment.
• Various methods of assessment of the autonomic tone, including heart rate variability, SKNA, and alternans, can be used as surrogate markers and predictors of the autonomic modulation treatment effect.
• Further research is warranted to optimize patient selection to maximize the efficacy of this novel therapeutic modality for cardiac arrhythmias.
The autonomic nervous system plays a central role in the pathogenesis of multiple cardiac arrhythmias, including atrial fibrillation and ventricular tachycardia. As such, autonomic modulation represents an attractive therapeutic approach in these conditions. Notably, autonomic modulation exploits the plasticity of the neural tissue to induce neural remodeling and thus obtain therapeutic benefit. Different forms of autonomic modulation include vagus nerve stimulation, tragus stimulation, renal denervation, baroreceptor activation therapy, and cardiac sympathetic denervation. This review seeks to highlight these autonomic modulation therapeutic modalities, which have shown promise in early preclinical and clinical trials and represent exciting alternatives to standard arrhythmia treatment. We also present an overview of the various methods used to assess autonomic tone, including heart rate variability, skin sympathetic nerve activity, and alternans, which can be used as surrogate markers and predictors of the treatment effect. Although the use of autonomic modulation to treat cardiac arrhythmias is supported by strong preclinical data and preliminary studies in humans, in light of the disappointing results of a number of recent randomized clinical trials of autonomic modulation therapies in heart failure, the need for optimization of the stimulation parameters and rigorous patient selection based on appropriate biomarkers cannot be overemphasized.
This work was supported by a grant-in-aid (#15GRNT23070001) and a mentored clinical/population research grant (#15MCPRP2579000) from the American Heart Association; the Institute of Precision Medicine (17UNPG33840017) from the American Heart Association; the RICBAC Foundation; and National Institutes of Health grants 1 R01 HL135335-01, 1 R21 HL137870-01, 1 R21EB026164-01, and 1U54GM10493. Dr. Singh has received consulting honoraria from Biotronik, Boston Scientific, Microport, EBR, Toray, Abbott, and Medtronic. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Kalyanam Shivkumar, MD, served as Guest Editor for this paper.
The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC: Clinical Electrophysiology author instructions page.
- Received December 9, 2019.
- Revision received February 6, 2020.
- Accepted February 14, 2020.
- 2020 American College of Cardiology Foundation
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