Case Study

Cardioneuroablation in a Young Patient With Severe Vasovagal Syncope

David Singh, MD

Chief, Department of Cardiovascular Diseases, The Queen’s Medical Center; Associate Professor of Medicine, John A. Burns School of Medicine; Honolulu, Hawaii

David Singh, MD

Chief, Department of Cardiovascular Diseases, The Queen’s Medical Center; Associate Professor of Medicine, John A. Burns School of Medicine; Honolulu, Hawaii

Vasovagal syncope (VVS) is the result of an exaggerated vagal response due to stimuli such as pain, prolonged standing, or emotional distress. Although the mechanisms underlying this disorder are not fully understood, enhanced vagal activity can result in vasodilation and/or bradycardia and subsequent syncope. Conventional treatment for VVS is often conservative and involves situational avoidance, volume expansion, and physical counterpressure maneuvers. However, these measures are ineffective in some patients and can result in severe impairment to a patient’s quality of life.

Because VVS episodes are often associated with a reduction in heart rate, there have been a number of trials that have examined the role of cardiac pacing for this condition.1 In most patients, asystole occurs late in the VVS after the blood pressure has already fallen. For this reason, pacemakers have had a limited role in treatment for this condition. There appears to be a limited role for permanent pacing in older patients with a significant cardioinhibitory response.1

Unfortunately, many patients suffering from VVS may not respond to traditional measures. Cardioneuroablation (CNA) has been proposed as a potential treatment strategy for patients with VVS who do not respond to standard treatment measures. This strategy involves catheter ablation of parasympathetic postganglionic neuron bodies from the endocardial surface of the atrial myocardium.2,3 This report details CNA in a patient with severe VVS.

Case Presentation

A 20-year-old female has a history of VVS dating back to 2015. She also has a history of seizure-like activity. EEGs failed to demonstrate epileptiform activity. It is suspected that many of these seizures were attributable to VVS episodes or pseudoseizure activity. Her workup was extensive and included upright tilt table testing, which was associated with syncope and a primary cardioinhibitory response without asystole. Fourteen-day ambulatory monitoring demonstrated periods of sinus bradycardia while awake with heart rates as low as 37 bpm. Echocardiogram and cardiac MRI were within normal limits. The patient self-reported 5-7 episodes of syncope or presyncope per week. She had extensive contact with the medical system. Between March 2020 and December 2020, she was seen in the emergency room or admitted to the hospital for syncope or seizure-like activity on 12 occasions. Numerous therapies were utilized to treat her condition including sodium tablets, beta blockers, scopolamine, midodrine, supplemental hydration, and counterpressure measures. None of these were effective at curbing her episodes. In December 2018, she underwent implantation of a BIOTRONIK dual-chamber pacemaker. This significantly helped to reduce her episodes. However, she developed persistent pain at the implant site, and the device was explanted in May 2020.

She was admitted to our medical center for syncope in December 2020. During this admission, she was observed to have resting heart rates in the 50s with bradycardia into the low to mid 30s during sleep, suggesting high vagal tone. A brief trial of theophylline was employed without success. We discussed CNA during a subsequent office visit. Given her severe symptoms and lack of response to traditional treatments, we elected to proceed with CNA.

Mapping and ablation of the ganglionated plexi (GP) was performed utilizing the protocol previously described by Aksu et al.4 The CARTO System (Version 7, Biosense Webster, Inc., a Johnson & Johnson company) was utilized. The PENTARAY multi-electrode mapping catheter (Biosense Webster) was used for electroanatomic mapping, and the THERMOCOOL SMARTTOUCH SF catheter (Biosense Webster) was utilized for ablation. The CardioLab Electrophysiology Recording System (GE Healthcare) was used with filter settings 200-500 Hz. Mapping of the right and left atrium was undertaken with a sweep speed of 200 mm/s. Ablation of the GPs was undertaken in the left atrium in the following order: left superior GP (LSGP), left inferior GP (LIGP), right superior GP (RSGP), right inferior GP (RIGP). Following this, the RSGP was mapped and ablated from the right atrial side. If areas of fractionation were identified (defined as low or high amplitude signals with ≥4 deflections from baseline), they were tagged as anatomic points on the mapping system. Areas of fractionation were confirmed manually using a 400 mm/s sweep speed.

The patient was unable to tolerate conscious sedation, and we converted to general anesthesia early on during the case. Baseline heart rate was 70 bpm; baseline blood pressure (following anesthesia induction) was 100/50; baseline PR interval was 187 milliseconds (ms). We identified a region of fractionation in the superior ridge area between the left upper pulmonary vein and the left atrial appendage (Figures 1 and 2). This was thought to correspond to the LSGP. Fractionation in the mid to lower ridge area was believed to correspond to the LIGP. Ablation in these regions was performed at 35 watts. No vagal response was observed with ablation in these regions, but it may have been masked by the presence of general anesthesia. A similar approach was undertaken in the region of the right GPs. The RSGP and RIGP were tagged and ablated (at 35 watts) outside the anterior right upper pulmonary vein and anterior right carinal regions, respectively. No vagal response was observed here. Ablation of the RSGP was then performed from the right side (posterior IVC/RA junction). Following ablation in this region, we noticed an immediate increase in the baseline heart rate to approximately 95 bpm. The blood pressure also increased to approximately 130/70. One mg of atropine was administered 2 times with 5 minutes between doses. No change in the heart rate was observed with either administration. Her PR interval was noted to decrease from 187 ms to 162 ms.

On follow-up, she was noted to have a heart rate of 92 bpm and a blood pressure in the 130/70s. She has also noted significant improvement in her symptoms. Since the procedure, she has had 3 additional episodes, although it is unclear whether these represented true syncopal events or pseudoseizure activity. Even if these were syncopal events, the frequency of events has been considerably reduced compared to her baseline prior to ablation.

Discussion

Perhaps the most challenging aspect of CNA is the identification of target GPs. Several approaches have been proposed. Anatomic ablation refers to empiric ablation of anatomical sites that are known to harbor GPs. The chief limitation of this approach is the variable locations of GPs among individuals, which in turn may compromise the accuracy and precision of the ablation. The use of high-frequency stimulation (HFS) to determine the location of GPs was first utilized in the setting of atrial fibrillation ablation.5 HFS with frequency of 20 Hz, voltage of 10-20 V, and pulse duration of 5 ms was delivered to each GP site.6 An elicited vagal response was utilized to mark the location of a GP.

The spectral guided GP ablation method was first introduced by Pachon et al.7 In this study, CNA was performed on a heterogenous patient population that included VVS, tachy-brady syndrome, and sinus node dysfunction. GPs were targeted using spectral analysis. Using spectral analysis software, they classified atrial myocardium into 2 categories. “Compact” myocardium was characterized by homogeneous spectrum resulting from a mass of very well-connected cells and frequencies of approximately 40 Hz. “Fibrillar” myocardium was thought to be the result of atrial myocardium with interspersed neural fibers. This myocardium was characterized by a fractionated and heterogenous spectrum with frequencies greater than 100 Hz.

Aksu et al simplified this protocol by targeting the fractionated electrograms in the anatomical GP locations.4 In their study, bipolar endocardial atrial electrograms were evaluated for amplitude and number of deflections at filter settings of 200-500 Hz. This was the approach employed in the case detailed in this report. One advantage of this approach is that it only requires standard electrophysiology equipment.

It is common to observe a vagal response during ablation of GPs. This may include asystole, PR prolongation, AV block, or slowing of the heart rate. Hu et al characterized the frequency of a vagal response during ablation.8 The most common site associated with a vagal response during ablation was the LSGP (observed 76% of the time). Vagal response was observed 45% of the time in the LIGP, 41% of the time with RSGP, and 37% of the time in the RIGP. It is important to note that general anesthesia can significantly blunt the vagal response to ablation. This may account for the absence of a vagal response during the aforementioned case. Aksu et al have also demonstrated that a right-side first strategy can result in an attenuation of vagal response during ablation of the LSGP and LIGP.4 We did observe an immediate increase in heart rate during ablation of the RSGP from the right side. This is consistent with the observations from Hu et al, who observed this phenomenon only in the setting of RSGP ablation.8

CNA appears to be a promising new therapeutic strategy for patients with VV syncope. It has also been utilized in patients with sinus node dysfunction as well as AV block.7 Like most emerging strategies, it needs to be subjected to rigorous evaluation ideally in the form of randomized controlled trials. As we await the results of this forthcoming research, it may be reasonable to adopt this approach in patients who have failed traditional therapies. Efforts to pool observational data from centers around the world are also underway and will undoubtedly help to inform future practice.

Conclusion

This report describes CNA in a patient with severe VVS refractory to standard interventions. Although more research needs to be performed to establish the role of CNA, it might be useful in cases such as the one described in this report. 

Contact the author on Twitter at @drdavidsingh

Acknowledgments: The author would like to thank Dr. Tolga Aksu for sharing his expertise and experience in preparing for the case outlined in this report.

Disclosures: The author has no conflicts of interest to report regarding the content herein.

References
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  2. Aksu T, Guler TE, Mutluer FO, Bozyel S, Golcuk SE, Yalin K. Electroanatomic-mapping-guided cardioneuroablation versus combined approach for vasovagal syncope: a cross-sectional observational study. J Interv Card Electrophysiol. 2019;54(2):177-188. doi: 10.1007/s10840-018-0421-4
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  7. Pachon JC, Pachon EI, Pachon JC, et al. “Cardioneuroablation”--new treatment for neurocardiogenic syncope, functional AV block and sinus dysfunction using catheter RF-ablation. Europace. 2005;7(1):1-13. doi: 10.1016/j.eupc.2004.10.003
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