Autonomic Modulation of Cardiac Arrhythmias: Methods to Assess Treatment and Outcomes

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.