Mechanistic refinement of non-invasive autonomic neuromodulation for cardiac arrhythmia

The autonomic nervous system has an important role in the pathogenesis of cardiac arrhythmias thus providing a critical opportunity for therapeutic intervention. Modulation of the autonomic nervous system has been attempted through numerous means including surgical sympathectomy, catheter-based ablation procedures, and transcutaneous approaches. Although autonomic innervation has been shown to have a significant effect on arrhythmogenicity, the complex network of interactions and the optimal strategies for interrupting this network are inadequately characterized. To further the field, this research will integrate established principles and techniques from neuroscience to study the role of autonomic neuromodulation in the treatment of cardiac arrhythmias. The investigation will focus on the ability of repetitive transcutaneous magnetic stimulation (TcMS) to modulate synaptic strength of autonomic cardiac innervation. The feasibility of this non-destructive and non-invasive technology is supported by Dr. Markman’s recent work published in JAMA targeting the cervical sympathetic chain with an inhibitory TcMS protocol in patients with ventricular tachycardia (VT) storm. The proposed research plan aims to improve understanding of the cardiac effects of autonomic neuromodulation, and to assess the efficacy of TcMS in patients with VT storm. Aim 1 seeks to characterize the cardiac electrophysiological effects of autonomic neuromodulation by invasively measuring conduction properties as well as levels of catecholamines and inflammatory cytokines before and after neuromodulation. This will develop critical tools for characterizing neural-cardiac interactions, allowing definitive assessment of their complex relationship. Aim 2 seeks to characterize the cardiac electrophysiological effects of autonomic neuromodulation by invasively measuring conduction properties as well as levels of catecholamines and inflammatory cytokines before and after neuromodulation. In combination, the findings from these aims will yield critical information regarding the mechanistic characterization of complex cardiac-neural pathways and help establish the role of a novel method of neuromodulation. In addition, this research will promote critically important continued interdisciplinary collaboration between neuroscientists and cardiovascular medicine. Dr. Markman, an early career investigator and a fellow in cardiac electrophysiology, has a long-term goal of establishing an independent research program in autonomic neuromodulation focused on mechanistically defining the complex neural circuits involved in cardiac arrhythmias. These research aims are part of a comprehensive training plan and will be supervised by a mentorship and advisory team consisting of national leaders in arrhythmia and neuroscience research and will guide his transition to an independently funded research career.