Intermittent Syncopal Atrioventricular Block With Normal Electrophysiology Study

Value of the Loop Recorder in Diagnosis and Efficacy of Cardioneuroablation in Treatment Without a Pacemaker

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EP LAB DIGEST. 2024;24(1):1,10-11,22.

Jose Carlos Pachon-M, MD, PhD, CCDS, FHRS, FLAHRS^1,2; Enrique I Pachon-M, MD, PhD^1,2; Juan Carlos Pachon-M, MD, PhD^1,2; Tomas G Santillana-P, MD²; Felipe Ortencio, MD²; Tasso J. Lobo, MD²; Carlos Thiene C Pachon, MD²; Christian Higuti, MD²; Juan Carlos Zerpa-A, MD²; Maria Zelia C. Pachon, MD²

¹São Paulo University, São Paulo, Brazil; ²São Paulo Heart Hospital, São Paulo, Brazil

Case Description

A 26-year-old woman without any significant family history began 10 years ago to experience repetitive episodes of transient loss of consciousness (presyncope and syncope) lasting 5-10 seconds, preceded by blurred vision. The symptoms were enough to prevent her from regular activities. Electrocardiogram (ECG), Holter monitoring, and treadmill tests were normal. The clinical cardiologist referred the patient for further investigation.

Laboratory screening demonstrated normal electrolytes and no infectious, inflammatory, or hormonal abnormalities were identified. Transthoracic echocardiogram showed mitral prolapse with discrete myxomatous degeneration and regurgitation. During the treadmill test, the patient reached the maximum heart rate without symptoms. The ECG was negative for ischemia, and there were no arrhythmias during or after exercise. Holter monitoring (24-hour) revealed normal sinus rhythm, no atrioventricular (AV) block, and an absence of significant arrhythmias. Additionally, 24-hour blood pressure monitoring was normal. Signal-averaged ECG showed normal QRS duration and no late potentials. Head-up tilt table testing was within normal parameters without symptoms. Cardiac magnetic resonance (MR) demonstrated preserved left ventricular ejection fraction as well as absence of late enhancement and other abnormalities.

An electrophysiology (EP) study was performed and all the baseline parameters of the His bundle electrogram were normal. Atrial or ventricular arrhythmias were not induced (with and without isoproterenol infusion), and programmed stimulation with up to 4 extrastimuli was performed from the right and left ventricles. An ajmaline test¹ was performed, which was negative for Brugada syndrome, and the dromotropic reserve of the His-Purkinje system was normal. Extracardiac vagal stimulation (ECVS)² showed long pauses due to sinus arrest and AV block when repeated during atrial stimulation at 70 beats per minute. These responses may be normal and deserve no treatment if not related to a spontaneous appearance. It was also noted that the vagal responses were eliminated by atropine infusion.

Since an abnormality to explain the clinical condition was not found, an implantable event monitor was indicated. After 2 weeks, the patient presented with syncope during low physical activity.

Interrogation of the event monitor showed intermittent AV block at the moment of the symptom (Figure 1). The AV block was considered functional, induced by the action of the autonomic nervous system, more specifically by transitory sympathetic plus vagal hyperactivity since no organic pathology of AV conduction was found.³

Therefore, cardioneuroablation (CNA)^4-8 (Figure 2) controlled by stepwise ECVS² was indicated with the purpose of attenuating the vagal action (Figure 3).

Discussion

This report highlights the case of a young patient with presyncope and syncope. The symptoms were so significant that they affected her daily activities. The clinical, electrocardiographic, and complementary exams did not reveal any abnormalities that justified the symptoms. MR and Experimental Data and Geometric Analysis Repository (EDGAR) imaging showed absence of fibrosis and/or pathological micropotentials. Furthermore, the EP study with pharmacological tests were not able to induce pathological AV block or ventricular tachyarrhythmias, which could have been a cause of the symptoms.

The only abnormality found in this case was the appearance of an intermittent AV block, registered by the implanted event monitor, which clearly reproduced the spontaneous symptoms (Figure 1). During the EP study, ECVS at the level of the jugular foramen² proved the integrity of the vagal innervation to be strong enough to cause asystole by sinus arrest and transient AV block, revealing full vagal activity over the sinus and AV nodes (Figure 3A-1). As the EP study had clearly demonstrated normal AV conduction, even with a large safety margin due to the normal response to ajmaline¹ (1 mg / kg body weight), we concluded that the most probable AV block origin would be a reflex cause, induced by episodic vagal hypertonia.³ Considering the abnormality revealed by the implanted loop recorder (Figure 1), the standard treatment would be pacemaker implantation. However, in view of the possibility of a functional origin, we considered that CNA could reduce the vagal action on the AV node and eliminate the risk of undesirable functional AV block.⁴ Both therapy options were explained to the patient and her family. It was also explained that a pacemaker would be indicated if the CNA were unsuccessful. After discussion, the patient decided on CNA.

The procedure was performed according to the technique previously described (Figure 2). Innervation was ablated (irrigated RF, 42W/s, 40^ºC, 30-60 s) by AF-Nests mapping based on fractionation plotting by the EnSite Velocity system (Abbott) and by eliminating the AF-Nests overlapping the anatomical regions of the main GP (Figure 2). Initially, ECVS was repeated (Figure 3-1), showing asystole by sinus arrest and high-grade AV block (Figures 3A-2 and 3A-3) when performed in conjunction with atrial pacing. After eliminating sinus node innervation, ECVS no longer showed sinus arrest, revealing only high-grade AV block (Figure 3B-4). Following extensive treatment of the GP3 and GP4 region, using biatrial access, there was complete disappearance of the induced AV block (Figure 3C-5). Thus, total acute vagal denervation was obtained and the procedure was concluded. Figures 3A-2, 3A-3, and 3B-4 show an intense vagal response before the denervation and complete, successful denervation at the end of CNA (Figure 3C-5). The anatomical regions of the GPs, in which there is a high density of overlapping AF-Nests, were extensively ablated. The most important objective was to eliminate the vagal action on the AV node, so the regions of GP3 and GP4 were more widely ablated. Right vagal stimulation was repeated until complete elimination of the vagal response. However, since the goal was to treat AV block, we also performed left vagal stimulation during atrial pacing to prove that AV block induction by vagal action no longer existed. This was considered the endpoint of the procedure. It is important to note that both right and left vagal stimulation are similar and cause sinus arrest and AV block; however, right is more effective in the sinus node, while left is more effective in the AV node.

Considering the complexity of the anatomic location, the high number of connections, and natural reinnervation, complete elimination of vagal action in the AV node is difficult to obtain and often depends on extensive CNA of the AF-Nests related to all 4 main GPs. This is because the AV node receives innervation from almost all GPs and the surrounding tissues have a large amount of intraparietal microneurons. Thus, it is essential that the CNA for the purpose of vagal denervation of the AV node is performed with stimulation of the left vagus nerve directly addressing GPs 2 (P point), 1, and 3. After this stage, if AV block induced by the vagus persists, it is also necessary to address the GP4, and eventually, the Waterston groove, as well as more AF-Nests outside the GP regions. In any case, it is essential to finish the procedure without a vagal response, considering that there is naturally a certain degree of reinnervation, and we must ensure that the attenuation of vagal reflexes remains in the long term.

The patient was followed up with for 55 months through regular clinical consultations every 6 months, with Holter and interrogation of the event monitor and through online transmission of events. During this period, she remained asymptomatic. Holter monitoring showed an absence of pauses with only rare ventricular extrasystoles. In addition, all queries from the event monitor and automatic transmissions showed no further pauses and no episodes of AV block. Since the procedure, the patient remains asymptomatic.

Conclusion

Syncope with normal EP study may be related to functional origin. Transitory AV block may occur even with normal invasive/pharmacological EP study. Tilt testing, Holter monitoring, and EP studies are not enough to elucidate the etiology in all cases. An insertable loop recorder can be helpful in these cases. Functional AV block may be successfully treated by CNA without pacemaker implantation. ECVS is fundamental to evaluate CNA step by step. An atropine test is also important to anticipate CNA outcome. 

Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest, and report no conflicts of interest regarding the content herein. Dr Jose Carlos Pachon-M reports US20190091475A1 patent is pending and participation on a data safety monitoring or advisory board for Biotronik and Medtronic.

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