Cardioneuroablation for the treatment of symptomatic bradycardia mediated by the cardiac autonomic nervous

Sinus bradycardia is a common clinical problem with a population prevalence of approximately 4/1000.^[1] Most patients are asymptomatic, but some patients experience symptoms such as fatigue, dizziness, exercise intolerance, syncope, or pre-syncope, worsening of angina symptoms, worsening of heart failure, or cognitive slowing. Although both European and American guidelines recommend cardiac pacing for patients with severe symptoms of sinus bradycardia, there are problems such as infection, electrode detachment, perforation, and pacemaker replacement.^[2,3]

The mechanism of symptomatic sinus bradycardia in young patients is still unclear. Our preliminary research has shown that ablation of atrial ganglionated plexus (GP) significantly improves sinus rhythm and suggests that abnormal autonomic nervous activity may play a role in the occurrence of symptomatic sinus bradycardia.^[4] To further elucidate the role of the cardiac autonomic nervous in the mechanism of sinus bradycardia and the long-term effects of cardioneuroablation on symptomatic sinus bradycardia patients, we recruited 73 with recurrent symptomatic sinus bradycardia that significantly impacted their daily lives from April 2015 to December 2018, excluding those with structural heart disease, any atrial or ventricular arrhythmias, drug-induced bradycardia, sinus pause > 2.0 s, positive atropine test, corrected sinus node recovery time (cSNRT) > 525 ms, or a history of cardiac ablation. After assessing sinus node function and 24-h Holter monitoring, the enrolled patients underwent either sequential ablation of all atrial GPs or simplified ablation targeting the RIGP and Ao-SVC GP (Figure 1). They were followed up for heart rate (HR), symptoms, and quality of life over a long-term period.

Figure 1.

Distribution of ablation points on the 3-dimensional endocardial surface of the left and right atrium.

Ablation sites are shown as red dots in yellow circles. Ao- SVC GP: aorta superior vena cava ganglionated plexus; LAO: left anterior oblique position; LIGP: left inferior ganglionated plexus; LL: left lateral position; LSGP: left superior ganglionated plexus; PA: posteroanterior position; RAGP: right anterior ganglionated plexus; RAO: right anterior oblique position; RIGP: right inferior ganglionated plexus.

The results showed that a total of 73 patients received either sequential (n = 46) or simplified (n = 27) GP ablation. During ablation, there was a significant increase in HR, which stabilized at 69.2 ± 6.5 beats/min after ablation, significantly higher than baseline (50.4 ± 4.1 beats/min) (P < 0.001). There was no significant difference in HR increase between the two ablation methods (19.5 ± 6.8 beats/min vs. 20.5 ± 5.9 beats/min, P = 0.485). With an average follow-up of 27.2 ± 17.4 months, the average HR of all patients remained significantly higher than baseline (61.7 ± 8.7 beats/min vs. 50.4 ± 4.1 beats/min, P < 0.001). Additionally, age was negatively correlated with HR increase (r = –0.687, P < 0.0001). HRV analysis after GP ablation revealed significant reductions in LF and LF/HF (P < 0.01), suggesting a decrease in parasympathetic activities. Based on this study, we found that autonomic nervous imbalance may be the pathophysiological basis of some symptomatic sinus bradycardia cases. GP ablation effectively increases sinus rhythm and improves the quality of life of symptomatic sinus bradycardia patients, with favorable long-term results, but its effectiveness is influenced by age. Moreover, the RIGP and Ao-SVC GP play a dominant role in parasympathetic activity. Although no post-ablation atrial arrhythmias were detected during follow-up, a simplified ablation approach may be preferred to avoid unnecessary injury.

Since Pachon, et al.^[5] first proposed it in 2005, cardiac vagal nerve ablation has been extensively researched by scholars as a potential treatment for neurally mediated syncope. However, there have been limited systematic studies on sinus bradycardia. In 2017, we published the first study proposing “cardiac autonomic nervous imbalance” as a potential mechanism for sinus bradycardia and systematically evaluated the efficacy of atrial GP ablation in the treatment of symptomatic sinus bradycardia (Figure 2). Our research gained extensive attention from international electrophysiology experts, including Douglas P. Zipes, who viewed it as a promising alternative to pacemaker therapy.^[6,7] This provides clues for uncovering the pathophysiological mechanisms of sinus bradycardia and the differential innervation of various GPs. Long-term follow-up results have confirmed that atrial GP ablation is an effective treatment for symptomatic sinus bradycardia patients with cardiac autonomic nervous imbalance and may serve as an alternative to or delay the need for pacemaker implantation.

Figure 2.

Schematic of “cardiac autonomic nervous imbalance” theory.