Treatment of Symptomatic Functional Atrioventricular Block by Cardioneuroablation as an Alternative to Pacemaker Implantation.

A woman with recurrent presyncope caused by a functional atrioventricular (AV) block after meals, with limiting symptoms, underwent cardioneuroablation and AV node vagal denervation without pacemaker implantation. Normal AV conduction was recovered with complete abolishment of symptoms. (Level of Difficulty: Advanced.).

Presentation

The patient was a 57-year-old woman who had begun to have recurrent episodes of presyncope after meals approximately 6 months earlier. She reported significant deterioration in her quality of life because of the constant need to control her diet and fear of unpredictable symptoms in public or in an unsupportive environment. The patient’s history included a thyroidectomy 3 years earlier, 2 cesarean sections, and an appendectomy. She also had a normal electrophysiological study (EPS) 3 years earlier because of asymptomatic sinus pause.

Learning Objectives

To understand that functional AV block by autonomic reflex is a common entity with challenging clinical management and that cases with limiting symptoms are typically treated with pacemaker implantation.

To realize that—rather than pacemaker implantation—AV block may instead be treated with cardioneuroablation, which uses endocardial ablation to achieve vagal denervation, eliminating the functional inhibition of the AV node without pacemaker implantation.

Investigation

Results of the patient’s resting electrocardiogram, echocardiogram, carotid Doppler, blood tests, and thyroid function were all normal. The 24-hour Holter monitoring showed a mean-minimum heart rate of 77/39 beats/min with periodic pauses of up to 2.6 seconds caused by a Mobitz II second-degree atrioventricular block (AVB), 2:1 conduction, and high-degree AVB after meals. In stress testing, the patient’s maximum heart rate was 141 beats/min with normal atrioventricular (AV) conduction. A 7-day loop recording showed several pauses in the heartbeat after meals caused by second-degree degree Mobitz II AVB, 2:1 conduction, and high-degree AVB without sinus depression, followed by pre-syncope (Figure 1). Invasive EPS was performed with pharmacologic testing. Basal EPS parameters were normal. The ajmaline challenge (1 mg/kg per 5 minutes intravenously [IV]) was negative for Brugada syndrome and showed normal His-Purkinje conduction. As expected, adenosine induced a 13-second AVB. Atropine (2 mg IV) showed a good response (heart rate from 55 to 75 beats/min and Wenckebach from 140 to 165 beats/min). Ventricular stability was normal. Thus, functional AVB was considered because organic AVB was ruled out. Therefore, cardioneuroablation (CNA) was indicated with the aims of AV node denervation and avoiding pacemaker implantation. The patient was informed of the risks and benefits of all therapeutic possibilities and agreed to the procedure.

Figure 1

7-Day Loop Recording Showing Symptomatic Paroxysmal High-Degree Atrioventricular Block After Meals

There is no PP interval modification.

Management

The CNA was performed under general anesthesia controlled by bispectral index monitoring. The procedure focused on AV node vagal denervation by anatomic landmarks with 3-dimensional (3D) electroanatomic fractionation mapping (Ensite Velocity, Abbott) to tag atrial fibrillation (AF) nests, mainly related to the third and fourth ganglionated plexus areas. Progressive denervation was controlled and confirmed by extracardiac vagus nerve stimulation (ECVS) (10 to 50 Hz/50 μs/70 V) (Figure 2) through the right and left internal jugular veins near the jugular foramen. Basal ECVS reproduced the AVB without and with atrial stimulation (Figure 3A). At the conclusion of the procedure, the ECVS was repeated, showing a reduction in the vagal response of the sinus node and the absence of an AV node response, completely eliminating the induced AVB and confirming the vagal denervation (Figures 3B and 3C). No further denervation of the sinus node was necessary. The final ablated points are shown in the 3D model in Figure 4.

Figure 2

Extracardiac Vagal Stimulation

(A) Neurostimulator. (B) Catheter progression within the internal jugular vein. (C) Close relationship of the vagus with the vein. (D) X-ray with the catheter placed at the left jugular foramen (yellow arrow).

Figure 3

Left Vagus Stimulation Pre- and Post-CNA

(A) Left vagus stimulation pre-cardioneuroablation (CNA), showing vagal atrioventricular block (AVB) without sinus node depression. (B) Left vagus stimulation post-CNA, showing no bradycardia and no AVB. (C) Left vagus stimulation post-CNA showing no AVB, even with high-frequency atrial pacing. A Pacing = atrial pacing; AV = atrioventricular; Brady = bradycardia; Stim = stimulation.

Figure 4

Atrial Fibrillation Nest Mapping of Sites of Cardioneuroablation Radiofrequency Application and Presumed Location of Ganglionated Plexuses

Red dots indicate sites of cardioneuroablation radiofrequency application and green dots indicate the presumed location of ganglionated plexuses in a 3-dimensional navigation system (Ensite Velocity, Abbott) obtained by atrial fibrillation nest mapping using fractionation software.

Follow-Up

At 24 months after the procedure, the patient remained totally asymptomatic, with normal sinus rhythm and absence of AVB on both the electrocardiogram and in serial 24-hour Holter monitoring, even after copious meals. No further AVB has occurred (Figure 5).

Figure 5

Holter Monitoring 24 Months Post-Cardioneuroablation Showing Normal Atrioventricular Conduction

AV = atrioventricular; HR = heart rate.

Discussion

Symptomatic AVB is a severe entity, which may be progressive and can confer a significant risk of falls, accidents, and sudden death. It has organic and functional causes. The latter presents the greatest clinical challenge because, despite its better prognosis, reversibility is not always achieved, and its intermittent and erratic presentation often makes treatment difficult, causing morbidity and lower quality of life. CNA was first proposed in the 1990s and published in 2004,, with the aim of treating functional bradyarrhythmias without pacemaker implantation. The goal was to achieve long-term partial vagal denervation through endocardial ablation of the postganglionic vagal neurons in atrial walls and in the epicardial ganglionic plexuses.,

Three fundamental steps of CNA are mapping of the neuromyocardial interface, demonstration of the vagal effect, and confirmation of vagal denervation. At the beginning, the neuromyocardial interface was accessed by online spectral mapping of AF nests,, giving rise to anatomic maps, which currently allow purely anatomic CNA to be performed by presuming the positions of the main ganglionic plexuses. However, owing to high interindividual variability, it is recommended that it be complemented by AF nest ablation. In a normal heart, these structures are directly related to innervation., They may be found by spectral mapping, conventional filtered recordings, or—more simply—by using the fractionation mapping software we developed in 2005,, which can tag potential innervation areas in a 3D electroanatomic model. The other fundamental steps of CNA, demonstration of the vagal effect pre-CNA (Figure 3A) and complete elimination of vagal action post-CNA, are easily achieved with ECVS by placing an EP catheter inside of the left internal jugular vein (Figure 2). The latter is the best endpoint for CNA (Figures 3B and 3C).

Thus, with CNA directed to the innervation of the AV node, it was possible to abolish reflex AV cardioinhibition,, and recover physiological nodal AV conduction, even long term. The patient’s symptoms were completely abolished without pacemaker implantation or any other additional treatment.

An intriguing aspect of this case is the selective functional AV block without any modification of the preceding sinus cycle (Figure 1). Some investigators have shown this AV block related to an increase in endogenous adenosine. However, in this case, it was possible to reproduce the same phenomenon by vagal action only through ECVS of the left vagus at a lower frequency (10 Hz) (Figure 6B). Typically, ECVS at a higher frequency causes sinus arrest (Figure 6A). These findings suggest that, in this specific case, the selective AVB is probably of cholinergic origin.

Figure 6

Selective AV Block Induced by Extracardiac Vagus Nerve Stimulation

Different responses to the extracardiac vagus nerve stimulation depending on the frequency. Left vagus stimulation at 10 Hz may reproduce the selective atrioventricular (AV) nodal inhibition without sinus depression.

Conclusions

CNA may be an effective treatment in patients with a symptomatic functional AV block, even with a proven positive adenosine hypersensitivity test. Further studies should be carried out to deepen the knowledge and further the development of this innovative therapy.

Funding Support and Author Disclosures

The authors have reported that they have no relationships relevant to the contents of this paper to disclose.