Electrophysiological study in Brugada syndrome: indications and prognostic value

Brugada syndrome is an inherited arrhythmic disorder associated with ventricular fibrillation, polymorphic ventricular tachycardia and sudden cardiac death, often in people without structural heart disease. Its electrocardiographic signature is a type 1 Brugada pattern: coved ST-segment elevation in the right precordial leads, particularly V1 and V2, recorded in standard or high intercostal positions. The pattern may be intermittent and can be unmasked by fever or sodium-channel blocker testing.

An electrophysiological study (EPS) can assess intracardiac conduction, programmed ventricular stimulation and inducibility of ventricular arrhythmias. Its role, however, is more nuanced than a simple positive-or-negative risk test. The clinical context, the ECG phenotype, symptoms, family history, genetic findings and the quality of the study protocol all influence interpretation.

For clinicians in Australia, this issue commonly arises when a patient presents to an emergency department after syncope, when a fever-related ECG raises concern, or when a family member has died suddenly. Referral pathways may involve a tertiary electrophysiology service in Sydney, Melbourne, Brisbane, Perth or Adelaide, while patients in regional Queensland, rural New South Wales or Western Australia may need to travel substantial distances.

The central question is whether EPS adds useful prognostic information beyond careful clinical assessment. Current evidence supports a selective, shared-decision approach rather than routine invasive testing for every person with a Brugada ECG pattern.

What the electrophysiological study evaluates

An EPS is performed in a cardiac catheterisation or electrophysiology laboratory under controlled conditions. Catheters are introduced through venous access, usually from the groin, and positioned in the right atrium, His bundle region and right ventricle. The study can document atrioventricular and intraventricular conduction, identify accessory pathways or other tachyarrhythmias, and deliver programmed ventricular extrastimuli.

In Brugada syndrome, the most discussed endpoint is inducibility of sustained ventricular tachycardia or ventricular fibrillation. Protocols vary according to the number of extrastimuli, the pacing site and the drive cycle length. Induction with one or two extrastimuli, particularly from the right ventricular apex and outflow tract, has generally been considered more specific than induction requiring three extrastimuli, although no protocol eliminates uncertainty.

The EPS may also reveal sinus node dysfunction, prolonged conduction intervals or clinically relevant supraventricular arrhythmias. These findings can support a broader understanding of an individual’s electrical phenotype, but they should not be treated as equivalent to proof that a spontaneous malignant ventricular arrhythmia will occur.

When an EPS may be appropriate

EPS is most often considered when the diagnosis or risk profile remains uncertain after a detailed history, serial ECGs and non-invasive assessment. A patient with unexplained syncope, especially syncope occurring at rest or during sleep and accompanied by a spontaneous type 1 pattern, may require comprehensive risk assessment. The procedure can be discussed when its result could influence ICD implantation or continued observation.

Patients with documented ventricular fibrillation or sustained ventricular tachycardia generally have a clear secondary-prevention indication for an implantable cardioverter-defibrillator, assuming the event was not caused by a reversible factor. In this setting, EPS rarely adds enough information to change the main management decision. Similarly, a patient with a spontaneous type 1 ECG and highly concerning arrhythmic syncope may already have a sufficiently high-risk clinical profile.

The role is less certain in an asymptomatic person with a drug-induced type 1 pattern. EPS may be offered in selected cases after discussion of its limitations, particularly when the patient has a concerning family history or wishes to understand whether inducible ventricular arrhythmia affects the management conversation. It is not generally justified as an automatic test for every fever-induced or incidental ECG abnormality.

Reading inducibility and non-inducibility

A positive ventricular stimulation study can identify a subgroup with a higher observed risk in some cohorts. The association is strongest when ventricular fibrillation or polymorphic ventricular tachycardia is induced using a relatively conservative protocol. Yet inducibility is not perfectly reproducible, and results can depend on pacing location, coupling intervals, sedation, autonomic tone and the experience of the laboratory.

A negative EPS should not be described as a guarantee of safety. Ventricular fibrillation may not be inducible during the procedure even though the patient remains at risk over time. This is particularly important when spontaneous type 1 ECG changes, arrhythmic syncope or a previous cardiac arrest are present. A reassuring study should support, rather than replace, longitudinal follow-up and advice about fever management.

The prognostic value of EPS has also been debated because studies have produced conflicting results. Earlier observational work suggested a strong relationship between inducibility and future ventricular arrhythmia, while later analyses and prospective data have found a weaker or inconsistent association. Differences in patient selection and stimulation protocols explain part of this variation.

Clinical features that carry greater weight

The history often provides more reliable prognostic information than an isolated EPS result. Survivors of cardiac arrest and patients with documented sustained ventricular arrhythmia are at the highest risk. Unexplained syncope that is abrupt, occurs without a clear prodrome and is compatible with an arrhythmic mechanism is more concerning than fainting after prolonged standing, venepuncture or dehydration.

A spontaneous type 1 Brugada ECG pattern generally carries more prognostic significance than a pattern visible only after ajmaline, flecainide or another sodium-channel blocker. The ECG should be interpreted carefully because right bundle branch block, early repolarisation, pectus deformity and lead placement can mimic or obscure the phenotype. Repeating V1 and V2 in the second or third intercostal spaces may improve detection.

Family history is relevant, particularly sudden unexplained death at a young age or a known pathogenic variant in a close relative. A pathogenic SCN5A variant may support the diagnosis and explain conduction disease in some families, but genetic testing does not provide a complete individual risk forecast. A negative genetic result also does not exclude Brugada syndrome.

Practical care in the Australian setting

Australian practice must account for geography and access. A person from the Northern Territory or far north Queensland may need retrieval or planned travel to a specialist centre for sodium-channel blocker challenge or EPS. The costs and disruption of travel, accommodation and time away from work can affect the decision to pursue an invasive test, particularly when the result is unlikely to alter treatment.

The public system and private hospitals may offer different waiting times and referral routes, and availability of an experienced inherited arrhythmia service is not uniform. Clear communication between the local cardiologist, emergency department and tertiary electrophysiologist is important. Patients often say they want a straightforward answer, but clinicians should explain that “positive” inducibility does not automatically mean an ICD is required.

Fever management deserves particular attention. Patients should receive a written plan to treat fever promptly with paracetamol where appropriate, seek medical review for significant or persistent fever, and avoid medicines known to aggravate sodium-channel dysfunction. Specialist resources and Australian medication advice should be checked because drug availability and brand names differ from those used overseas.

Lifestyle counselling should be practical rather than alarmist. Excessive alcohol intake, recreational drugs, sleep deprivation and extreme physiological stress may increase arrhythmic vulnerability in some individuals. Families should understand CPR, automated external defibrillator use and when to call triple zero. These measures remain important whether or not an EPS has been performed.

Integrating EPS into shared decision-making

The decision to proceed should begin with a clear clinical question: will the EPS help clarify diagnosis, identify another arrhythmia, or change the balance between ICD implantation and observation? If the answer is uncertain, the patient should hear about procedural risks, sedation, vascular complications, radiation exposure and the possibility of an inconclusive result.

An ICD can prevent sudden death from ventricular fibrillation, but implantation carries long-term consequences, including inappropriate shocks, lead failure, infection and psychological distress. For a young adult, device longevity, employment, driving, sport and future lead management matter. EPS should therefore be considered within a broader risk discussion, not as a stand-alone decision rule.

Follow-up may include periodic ECGs, review after febrile illness, assessment of new syncope or palpitations, and family screening where appropriate. New symptoms can change the risk assessment even after a previously negative study. Arrhythmia specialists can also revisit the diagnosis when the ECG phenotype evolves or when a competing explanation becomes apparent.

Clinicians and researchers can compare evolving evidence through the journal’s arrhythmia collections, where focused material on Brugada syndrome, ventricular arrhythmia and inherited electrical disease can support continuing education. For Australian trainees, this broader perspective is valuable because recommendations must be applied across metropolitan centres, regional hospitals and varied patient circumstances.

An EPS has greatest value when it is technically rigorous and interpreted alongside the whole patient. Inducible ventricular arrhythmia may strengthen concern in a borderline case, while non-inducibility should not erase high-risk clinical features. The most defensible approach combines phenotype, symptoms, family history, genetics, patient preferences and expert electrophysiology review.

Researchers and clinicians with relevant data, reviews or case-based insights can consult the journal’s author information when preparing work for peer review. Continued Australian and Asia-Pacific research is needed to refine stimulation protocols, clarify the prognostic role of inducibility and improve equitable access to inherited arrhythmia expertise.