Syncope recurrence and long-term heart rate variability after cardioneuroablation for vasovagal syncope: a systematic review and meta-analysis
Authors: Vandenberk B , Lei L Y , Ballantyne B , Vickers D , Liang Z , Sheldon R S , Chew D S , Aksu T , Raj S R , Morillo C A 
Published: October 2022

Abstract

Background
Cardioneuroablation (CNA) has emerged as a promising therapy in patients with refractory vasovagal syncope (VVS). Well-designed randomized clinical trials (RCT) are lacking.

Purpose
To provide an estimate of the procedural success rate of CNA, including subgroup analysis by method and target of ablation, as well as serial measurements of autonomic tone after CNA with heart rate variability (HRV).

Methods
A systematic search of studies was performed in MEDLINE and EMBASE according to the PRISMA guidelines, from inception to 14 February 2022. Observational studies and clinical trials reporting success rates were included. Quality assessment was performed using the CONSORT and STROBE recommendations. The primary outcome was freedom from syncope after CNA. Meta-analysis was performed with a random-effects model. The secondary outcome was serial HRV analysis (heart rate, SDNN, rMSSD and LF/HF ratio) analysed with one-way ANOVA with Bonferroni's correction for multiple testing.

Results
A total of 465 patients were included across 14 studies (mean age 40±4 years; 54% females). All included studies were of intermediate quality (median 17, IQR 16–18). Procedural approach to CNA was variable: 50 patients (10.8%) by mapping of fractionated electrograms, 73 patients (15.7%) with the spectral method, 210 (45.2%) with high frequency stimulation, 73 (15.7%) with a purely anatomically guided method, and 59 patients (12.6%) with a combination. The target was bi-atrial in 168 patients (36.1%), left atrium only in 259 patients (55.7%), and right atrium only in 38 patients (8.2%).
The freedom from syncope was 91.9% (95% CI 88.1–94.6%; I2=6.9%, p=0.376; Figure 1). CNA limited to right atrial ablation was associated with a significantly lower success rate (p&lt;0.0001; 81.5%, 95% CI 51.9–94.7%) versus left atrial ablation only (94.0%, 95% CI 88.6–96.9%) and bi-atrial ablation (92.7%, 95% CI 86.8–96.1%). Subgroup analysis according to the technique used to identify GPs did not show any significant difference in success rate (p=0.206).
Ten studies (n=317, 68.2%) reported at least one HRV parameter. Results are presented in Figure 2 with the mean and standard deviations. There were significant increases in heart rate, and significant decrease in SDNN, rMSSD and LF/HF ratios for each follow-up timepoint available (p&lt;0.0001 for all analyses). Recovery of these parameters was observed in 2 studies, but these were not associated with an increased risk in syncope recurrence.

Conclusion
This meta-analysis suggests a high procedural success rate of CNA in VVS of 92%. CNA induces long-term changes in HRV, however some studies reported recovery of these parameters without an association with syncope recurrence. Therefore, HRV changes may not be an appropriate surrogate endpoint for clinical response. Well-designed double-blind, multi-center sham controlled RCTs are needed to provide evidence for future treatment guidelines.

Funding Acknowledgement
Type of funding sources: Foundation.