Persistent Proarrhythmic Neural Remodeling Despite Recovery From Premature Ventricular Contraction-Induced...

Area of Science:

• Cardiology
• Neuroscience
• Physiology

Background:

• The neural remodeling in premature ventricular contraction-induced cardiomyopathy (PVC-CM) is not well understood.
• Investigating neural changes is crucial for understanding PVC-CM pathophysiology and developing targeted therapies.

Purpose of the Study:

• To characterize cardiac sympathovagal balance and proarrhythmia in a canine model of PVC-CM.
• To determine the role of neural remodeling in the development and persistence of arrhythmias associated with PVC-CM.

Main Methods:

• A canine model was developed using 12 animals with epicardial pacemakers and radiotelemetry to record cardiac rhythm and nerve activity (NA).
• Bigeminal premature ventricular contractions (PVCs) were induced for 12 weeks, followed by a 4-week recovery period.
• Measurements included left ventricular ejection fraction (LVEF), cardiac contractility (dP/dT), sympathetic neural activity (SNA), vagal nerve activity (VNA), and heart rate (HR) variability (HRV).

Main Results:

• PVC-CM induction led to decreased LVEF and dP/dT, with increased resting and exercise SNA, VNA, and HR, and decreased HRV.
• Increased SNA preceded atrial and ventricular arrhythmias, which were abolished by clonidine.
• Despite LVEF and VNA recovery after PVC cessation, persistent SNA, altered HR, HRV, and proarrhythmia were observed, alongside sympathetic hyperinnervation in the stellate ganglia.

Conclusions:

• Neural remodeling in PVC-CM is marked by persistent extracardiac sympathetic hyperinnervation and hyperactivity, even after LVEF normalization.
• The altered cardiac sympathovagal balance acts as a critical trigger and substrate for atrial and ventricular proarrhythmia in PVC-CM.