Sudden cardiac death (SCD) due to ventricular arrhythmias is the leading cause of mortality in the United States, resulting in 250,000 deaths/year. The autonomic nervous system plays a major role in the pathophysiology of arrhythmias leading to SCD and neuraxial modulation provides an important venue for therapeutic intervention. The major goal of our research is to investigate the role of cardiac sympathetic innervations in the genesis of arrhythmias, and that of neuraxial modulation in prevention of these arrhythmias in humans. The mechanisms underlying sympathetic control of myocardial excitability in normal and diseased human hearts, and specifically, regional differences (apex versus base, epicardium versus endocardium, right versus left stellate ganglion innervation) remain unknown and need to be studied. Further, myocardial scars seen in ischemic and non-ischemic cardiomyopathy show nerve sprouting at the border zone of scars due to neural remodeling, which has been implicated in the pathophysiology of ventricular arrhythmias. The functional effects of nerve stimulation in this setting and how neuraxial blockade works in humans in these diseases are still unknown and this knowledge can help guide therapy. In this proposal, electrophysiological effects of direct regional cardiac nerve stimulation and neuraxial modulation of the thoracic sympathetic ganglia will be investigated. Areas of the heart regulated by the right and left stellate ganglia will be delineated in patients undergoing interventional electrophysiology procedures and cardiac transplantation. Understanding neuraxial modulation has the potential to further develop therapies that target these pathways in the very near term. Therapies such as right, left, or bilateral cerviocothoracic sympathectomy which has been 're-introduced'into clinical practice (by our group and others) already show a lot of promise and could emerge as novel/elegant therapies that are also cost-effective for the prevention of SCD. Therefore, neuraxial modulation is an approach that has the potential to have a global impact given the prohibitive high cost and morbidity associated with implantable defibrillators which prevent their expanded use.

Public Health Relevance

The project seeks to identify the pathways that regulate sympathetic output to the heart and study its modulation and role in ventricular arrhythmias. Ventricular tachycardia and fibrillation are thought to be the major cause of sudden cardiac death resulting in over 250,000 deaths/year in the USA. By defining the regulation of these nerves in humans we can improve the treatment of these arrhythmias and prevent sudden cardiac death.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
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Special Emphasis Panel (ZRG1-CVRS-E (02))
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Lathrop, David A
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University of California Los Angeles
Internal Medicine/Medicine
Schools of Medicine
Los Angeles
United States
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Methangkool, Emily; Chua, Jason H; Gopinath, Anupama et al. (2014) Anesthetic considerations for thoracoscopic sympathetic ganglionectomy to treat ventricular tachycardia storm: a single-center experience. J Cardiothorac Vasc Anesth 28:69-75
Arshad, Aysha; Johnson, Christopher K; Mittal, Suneet et al. (2014) Comparative safety of periablation anticoagulation strategies for atrial fibrillation: data from a large multicenter study. Pacing Clin Electrophysiol 37:665-73
Remo, Benjamin F; Preminger, Mark; Bradfield, Jason et al. (2014) Safety and efficacy of renal denervation as a novel treatment of ventricular tachycardia storm in patients with cardiomyopathy. Heart Rhythm 11:541-6
Bradfield, Jason S; Homsi, Mohamed; Shivkumar, Kalyanam et al. (2014) Coupling interval variability differentiates ventricular ectopic complexes arising in the aortic sinus of valsalva and great cardiac vein from other sources: mechanistic and arrhythmic risk implications. J Am Coll Cardiol 63:2151-8
Miller, John M; Kowal, Robert C; Swarup, Vijay et al. (2014) Initial independent outcomes from focal impulse and rotor modulation ablation for atrial fibrillation: multicenter FIRM registry. J Cardiovasc Electrophysiol 25:921-9
Lynch 3rd, Joseph P; Hwang, Jennifer; Bradfield, Jason et al. (2014) Cardiac involvement in sarcoidosis: evolving concepts in diagnosis and treatment. Semin Respir Crit Care Med 35:372-90
Vaseghi, Marmar; Gima, Jean; Kanaan, Christopher et al. (2014) Cardiac sympathetic denervation in patients with refractory ventricular arrhythmias or electrical storm: intermediate and long-term follow-up. Heart Rhythm 11:360-6
Yamakawa, Kentaro; So, Eileen L; Rajendran, Pradeep S et al. (2014) Electrophysiological effects of right and left vagal nerve stimulation on the ventricular myocardium. Am J Physiol Heart Circ Physiol 307:H722-31
Bradfield, Jason S; Vaseghi, Marmar; Shivkumar, Kalyanam (2014) Renal denervation for refractory ventricular arrhythmias. Trends Cardiovasc Med 24:206-13
Khalsa, Sahib S; Shahabi, Leila; Ajijola, Olujimi A et al. (2014) Synergistic application of cardiac sympathetic decentralization and comprehensive psychiatric treatment in the management of anxiety and electrical storm. Front Integr Neurosci 7:98

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