Cardioneuroablation for vasovagal syncope: an evidence update

Vasovagal syncope remains one of the commonest causes of transient loss of consciousness encountered in emergency departments and outpatient cardiology clinics. In Australia, where large public hospitals such as Royal Melbourne and Royal Prince Alfred assess thousands of patients each year for unexplained blackouts, the search for a durable interventional therapy has gained real momentum. While conventional strategies such as hydration, physical counterpressure manoeuvres and pacing have their place, a growing body of research has begun to clarify whether ablating the intrinsic cardiac autonomic ganglia can meaningfully reduce recurrent events in patients with refractory reflex syncope.

The technique most often discussed in the current literature is ganglionic plexus ablation, sometimes called cardioneuroablation when performed for vagally mediated bradyarrhythmias. It targets the neural networks embedded in the atrial epicardium that mediate the cardioinhibitory and vasodepressor responses responsible for the classic faint. Recent editorials and themed collections on the topic have brought renewed attention to where this therapy sits in the contemporary treatment algorithm, particularly for younger patients with frequent, recurrent and unmistakeably cardioinhibitory episodes.

The interest from electrophysiologists on this continent is not purely academic. Australian centres have contributed substantially to multicentre registries, and several investigators here have helped refine the technique, with reproducible ablation protocols emerging from groups in Melbourne, Sydney and Adelaide. Procedural uptake has nonetheless been cautious, partly because the randomised data remain limited and partly because local funding models require clear evidence of clinical benefit before a procedure can be listed on the Medicare Benefits Schedule as a rebatable item.

This article reviews the most recent evidence for the procedure, summarises patient selection criteria used in published studies, and considers how the data align with current Australian Heart Rhythm Society and CSANZ practice. It also touches on the gaps that remain before this becomes a routinely recommended option for the average patient fainting in an Adelaide shopping centre or a Perth heatwave.

Pathophysiology and the rationale for autonomic modulation

The clinical pattern of vasovagal syncope arises from a paroxysmal exaggeration of normal reflexes. Triggers such as prolonged standing, emotional distress, venepuncture or dehydration, the last being particularly common across much of inland Australia during the summer months, provoke a sudden shift in autonomic balance. Sympathetic withdrawal and parasympathetic surge produce bradycardia, hypotension, or both, culminating in cerebral hypoperfusion and the familiar prodrome.

The intrinsic cardiac autonomic nervous system, including the ganglionated plexi clustered at the posterior left atrium, the pulmonary vein antra and the inferior vena cava–left atrial junction, acts as the final common pathway for these reflexes. High-frequency stimulation of these regions produces reproducible vagal responses, the so-called vagal response, which has become the cornerstone of functional mapping during ablation procedures.

The interventional logic behind denervation is straightforward: if these ganglia initiate or amplify the reflex, modifying them with radiofrequency energy should blunt the response. Early observations in patients undergoing atrial fibrillation ablation who also had a history of reflex syncope provided the first clinical signal that empirical ganglion plexus modification could reduce syncope burden over the medium term.

Evidence from recent trials and registries

The most discussed randomised evidence comes from a series of trials, the largest being ROMANA, that compared endocardial cardioneuroablation against standard therapy in patients with recurrent reflex syncope. Patients in the ablation arms experienced markedly fewer syncopal events over follow-up periods ranging from twelve to thirty months. The freedom-from-recurrence curves diverged early and continued to widen, suggesting a sustained physiological effect rather than a placebo response.

Observational registries from European and Asian centres broadly agree on direction, although effect sizes vary with case mix. Older patients, those with predominantly vasodepressor responses, and those with significant medical comorbidities tend to show smaller benefit, while younger patients with purely cardioinhibitory responses captured on implantable loop recorder demonstrate the largest absolute reduction in recurrent syncope.

A useful complementary perspective has come from studies of pacing-induced cardiomyopathy, which explore an adjacent side of autonomic modulation. Reviewing the pacing-induced cardiomyopathy article highlights how pacing alters cardiac neural traffic and why non-pharmacological, ganglion-targeted approaches may offer advantages over permanent device implantation.

Patient selection and procedural approach

Appropriate selection is currently the strongest predictor of a satisfactory outcome. Most published protocols require a documented spontaneous or tilt-table positive episode together with bradycardia captured on an implantable loop recorder or ambulatory monitor, a pattern that Australian cardiologists frequently refer to as the cardioinhibitory subtype. Younger patients with a long anticipated duration of symptoms also tend to be prioritised, because the cumulative benefit profile of ablation is more attractive over decades than over years.

The procedural approach typically involves electroanatomical mapping of the left atrium via a transseptal approach, with high-frequency stimulation used to localise the target ganglia. Ablation is delivered endocardially, although a small number of centres have reported epicardial access via subxiphoid puncture for refractory cases. Procedural duration in the published series ranges from ninety minutes to just over two hours, with complication rates comparable to standard atrial fibrillation ablation.

In Australian practice, screening usually occurs in a dedicated syncope clinic, often run jointly by cardiology and neurology. The work-up commonly includes a head-up tilt test, an implantable loop recorder for borderline cases, and a careful review of medications such as antihypertensives that may amplify the reflex. Patients are counselled that the procedure is elective and that outcomes depend strongly on the underlying physiology.

Comparison with pacing and conservative therapy

For decades the only non-pharmacological option for recurrent cardioinhibitory vasovagal syncope was pacemaker implantation. Closed-loop stimulation pacing systems are now widely used across Australian tertiary centres and can reduce syncope frequency by roughly two-thirds in appropriately selected patients. The cost and small but real risk of long-term device complications have nevertheless motivated a search for less invasive alternatives.

Indirect comparisons suggest that cardioneuroablation and pacing produce broadly similar reductions in syncope burden at one to two years, with ablation avoiding device-related infection, lead extraction concerns and the cosmetic considerations that patients in their twenties and thirties often raise. Pacing retains an advantage in older patients with unpredictable, sudden-onset asystole, where the immediate availability of back-up rate response cannot be matched by any ablation strategy currently available.

Conservative therapy remains first-line for most patients. Education on trigger avoidance, salt and fluid loading in selected cases, and physical counterpressure manoeuvres such as leg crossing and squatting are effective in around half of patients referred to syncope clinics. The challenge is identifying the remaining half who continue to faint despite optimal conservative management, and this is where newer interventional strategies fit into a shared decision-making conversation.

Outstanding questions and research priorities

Several questions remain before the therapy becomes standard of care. The long-term durability of denervation is not yet fully characterised, with some series suggesting partial reinnervation beyond three years. Optimal endpoints for ablation, whether complete elimination of all vagal responses versus targeted modification of dominant sites, remain an area of active investigation, with no clear consensus across guidelines. Standardised reporting of non-fatal pre-syncopal events would also help clarify the overall clinical impact rather than the narrow binary of syncope versus no syncope.

Australian contributions to upcoming multicentre trials are likely to help answer these questions. Centres here have the volume, the imaging infrastructure and the familiarity with autonomic testing required to recruit meaningfully into international studies. Continued engagement with the broader community through resources such as the journal's themed journal collections will also help clinicians stay current as the evidence base matures.

In Australian practice today, proceduralists are increasingly comfortable offering cardioneuroablation to the right patient, with the right physiology, after the right work-up. The technique is no longer experimental but it is not yet routine, and the conversations between electrophysiologist and patient have evolved to reflect that nuance.

If you are managing patients with recurrent vasovagal syncope and want to refine your patient selection approach, explore the latest themed collections on cardiac autonomic modulation and consider submitting your own case series or registry data to the Journal of Arrhythmia. Sharing local experience will help move the evidence base from promising to definitive.