Effect of Bilateral Cardiac Sympathetic Denervation on Burden of Premature Ventricular Contractions

The autonomic nervous system plays a crucial role in the pathogenesis of ventricular tachyarrhythmias (VT/VF). Neuromodulatory interventions, such as cardiac sympathetic denervation (CSD), have proven beneficial in the treatment of ventricular tachycardia (VT) storm and implantable cardioverter defibrillator (ICD) shocks refractory to medical therapy and catheter ablation.¹ Although sympathetic stimulation has been reported to cause early and late after depolarization in animal models,^2,3 data on the effects of CSD on burden of premature ventricular contractions (PVCs) are lacking. The objective for this study was to characterize the impact of bilateral CSD on PVC burden.

Retrospective data review was approved by the UCLA Institutional Review Board. All deidentified data will be made available upon written request as long as HIPAA compliance can be maintained. Data from 92 patients who underwent bilateral CSD from 2010 to 2021 at a single center for treatment of refractory VT or VT storm were reviewed. Details of the CSD procedure have been previously reported.¹ Only patients with ICD interrogation reports and/or ambulatory monitors documenting PVC burden before and after bilateral CSD, without further interval catheter ablation of PVC or VT post-CSD, were included. Daily PVC burden calculated from these reports. Pertinent clinical characteristics, such as left ventricular ejection fraction (LVEF), beta-blocker and antiarrhythmic drug (AAD) therapy, and appropriate ICD shocks were also collected. Continuous variables are summarized as median and interquartile range (IQR). Pre- and post-procedure comparisons of beta-blocker and AAD therapy, LVEF, PVC burden, and ICD shocks or sustained VT episodes were performed using Wilcoxon signed rank tests with p<0.05 considered significant.

Thirty-six patients (56.6±13.6 years old, 81% male, 86% non-ischemic cardiomyopathy, 2.0±1.6 prior VT ablations) had device or monitor reports with documented PVC burden at a median of 36 days (IQR 15–102) before and 99 days (IQR 40–158) after CSD. Approximately 94% and 92% of patients were on beta-blocker therapy both before and after CSD, respectively, of which 25% decreased and 14% increased their dose post-CSD. AAD use was also similar pre vs. post CSD, with 75% of patients on at least one AAD and 47% on amiodarone prior to the procedure, compared to 81% on at least one AAD and 47% on amiodarone therapy after CSD. Average dose of amiodarone before and after CSD was also similar at 335 vs. 305 mg per day, respectively.

Daily PVC burden was significantly reduced in average by 59% following CSD (Figure 1), from median of 1,108 (IQR 446–3,255) to 471 PVCs/day (IQR 102–2,120, p=0.01). As PVC burden in the overall cohort was relatively low, a subgroup analysis of 7 patients (49.3±9.2 years old, 71% male, 71% non-ischemic cardiomyopathy) who had greater than 4,000 PVCs/day was performed. These patients had a median daily PVC burden of 13,471 (IQR 7,449–19,227) at baseline, which decreased substantially after CSD to 6,730 (IQR 3,610–8,203), p=0.02.

Figure 1.

Bilateral CSD was associated with significant reductions in PVC burden and ICD shocks/sustained VT episodes. In the subset of patients with a higher burden (> 4000 PVCs/day), CSD was associated with greater decrease in PVC burden. Box and whisker plots represent median and interquartile ranges, x = sample mean.

ICD shock data at a median follow up of 365 days (IQR 217.5–365) was reduced in average by 78% (median of 0.5, IQR 0–2) compared to the year prior to CSD (median of 5, IQR 3–13, p<0.001). Two patients died and two underwent heart transplantation. There was no significant change in LVEF pre vs. post-CSD in the overall cohort (median of 38% (IQR 29–51) vs. 37% IQR (26–48) p=0.1) or in the subset of 7 patients with a higher burden of PVCs (median of 42% (IQR 34–53) pre vs. 43% (IQR 34–47) post, p=0.4).

To the best of our knowledge, this is the first study to evaluate the effects of CSD on PVCs, demonstrating that bilateral CSD is associated with a significant reduction in overall PVC burden. Furthermore, in patients with a higher baseline PVC burden, bilateral CSD was associated with an even greater reduction. These clinical findings are consistent with mechanistic studies suggesting that a heightened sympathetic tone contributes to the pathogenesis of ventricular ectopy.^{2, 3} The results suggest that bilateral CSD may be considered as a treatment strategy for patients with refractory PVCs or PVC-induced polymorphic VT/VF despite maximal medical therapy in whom the site(s) of origin of PVCs may be multifocal or inaccessible with catheter ablation. The current study has limitations, including the small sample size and its retrospective nature. In addition, in this population with in ischemic and non-ischemic cardiomyopathy, CSD was not specifically performed for PVCs. Larger studies are required to further validate these findings, and specifically, evaluate benefit in patients with PVC-induced cardiomyopathy. However, the results of this study provide important initial insights, suggesting that the procedure could be beneficial for reducing PVC burden.

Nonstandard Abbreviations and Acronyms

AAD

Anti-arrhythmic drug

CSD

cardiac sympathetic denervation

ICD

implantable cardioverter-defibrillator

IQR

interquartile range

LVEF

left ventricular ejection fraction

PVC

premature ventricular contraction

VT

ventricular tachycardia

VT/VF

ventricular tachyarrhythmias