Author + information
- Received July 11, 2019
- Revision received September 30, 2019
- Accepted October 21, 2019
- Published online January 6, 2020.
- Alex Y. Tan, MDa,b,∗ (, )@RichmondVAMC,
- Khalid Elharrif, MDa,b,
- Ricardo Cardona-Guarache, MD, MPHa,b,
- Pranav Mankad, MDa,b,
- Owen Ayers, BAb,
- Martha Joslyn, MSb,
- Anindita Das, PhDa,
- Karoly Kaszala, MD, PhDa,b,
- Shien-Fong Lin, PhDc,
- Kenneth A. Ellenbogen, MDa,b,
- Anthony J. Minisi, MDa,b and
- Jose F. Huizar, MDa,b
- aPauley Heart Center, Virginia Commonwealth University, Richmond, Virginia
- bElectrophysiology Section, Division of Cardiology, Hunter Holmes McGuire VA Medical Center, Richmond, Virginia
- cKrannert Institute of Cardiology, Indiana University School of Medicine, Indianapolis, Indiana
- ↵∗Address for correspondence:
Dr. Alex Y. Tan, Electrophysiology Section, Division of Cardiology, Hunter Holmes McGuire VA Medical Center, 1201 Broad Rock Blvd, Richmond, VA 23220.
Background The presence and significance of neural remodeling in premature ventricular contraction-induced cardiomyopathy (PVC-CM) remain unknown.
Objectives This study aimed to characterize cardiac sympathovagal balance and proarrhythmia in a canine model of PVC-CM.
Methods In 12 canines, the investigators implanted epicardial pacemakers and radiotelemetry units to record cardiac rhythm and nerve activity (NA) from the left stellate ganglion (SNA), left cardiac vagus (VNA), and arterial blood pressure. Bigeminal PVCs (200 ms coupling) were applied for 12 weeks to induce PVC-CM in 7 animals then disabled for 4 weeks to allow complete recovery of left ventricular ejection fraction (LVEF), versus 5 sham controls.
Results After 12 weeks of PVCs, LVEF (p = 0.006) and dP/dT (p = 0.007) decreased. Resting SNA (p = 0.002) and VNA (p = 0.04), exercise SNA (p = 0.01), SNA response to evoked PVCs (p = 0.005), heart rate (HR) at rest (p = 0.003), and exercise (p < 0.04) increased, whereas HR variability (HRV) decreased (p = 0.009). There was increased spontaneous atrial (p = 0.02) and ventricular arrhythmias (p = 0.03) in PVC-CM. Increased SNA preceded both atrial (p = 0.0003) and ventricular (p = 0.009) arrhythmia onset. Clonidine suppressed SNA and abolished all arrhythmias. After disabling PVC for 4 weeks, LVEF (p = 0.01), dP/dT (p = 0.047), and resting VNA (p = 0.03) recovered to baseline levels. However, SNA, resting HR, HRV, and atrial (p = 0.03) and ventricular (p = 0.03) proarrhythmia persisted. There was sympathetic hyperinnervation in stellate ganglia (p = 0.02) but not ventricles (p = 0.2) of PVC-CM and recovered animals versus sham controls.
Conclusions Neural remodeling in PVC-CM is characterized by extracardiac sympathetic hyperinnervation and sympathetic neural hyperactivity that persists despite normalization of LVEF. The altered cardiac sympathovagal balance is an important trigger and substrate for atrial and ventricular proarrhythmia.
- autonomic nervous system
- idiopathic ventricular arrhythmia
- nonsustained ventricular tachycardia
Dr. Tan receives research grants from American Heart Association (AHA SDG 16SDG31280012). Dr. Huizar has received research grants from National Institutes of Health (1R56HL133182-01); and has received research support from St. Jude Medical. Dr. Kaszala has received research support from Boston Scientific Corp and St. Jude Medical. Dr. Ellenbogen has received research support from Boston Scientific, Biosense Webster, Medtronic, St. Jude Medical; is a consultant for Boston Scientific, St. Jude Medical, Atricure, and Medtronic; and has received honoraria from Medtronic, Boston Scientific, Biotronik, Biosense Webster, and Atricure. All other authors have reported that they have no relationships relative to the contents of this paper to disclose.
- Received July 11, 2019.
- Revision received September 30, 2019.
- Accepted October 21, 2019.
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