Brugada syndrome (BrS) is a genetic heart rhythm disorder, or channelopathy, that predisposes individuals to life-threatening abnormal heart rhythms, often occurring during sleep or rest. Diagnosis relies heavily on recognizing a distinctive pattern on an electrocardiogram (ECG), which reflects an issue with the heart’s electrical system, specifically the sodium channels. The inherent difficulty in diagnosing this condition stems from the fact that the characteristic ECG pattern can be intermittent, meaning it appears and disappears spontaneously. Furthermore, various other conditions and transient factors can produce an identical ECG pattern, making misdiagnosis a significant concern that requires specialized evaluation.
The Core Diagnostic Criteria
The definitive diagnosis of Brugada syndrome requires the presence of the Type 1 ECG pattern. This pattern must be observed in the right precordial leads (V1 and V2), which are often placed higher on the chest wall for assessment. The Type 1 pattern is characterized by a “coved” ST-segment elevation of at least two millimeters, descending into a negative T-wave. This coved pattern is the only one considered diagnostic for Brugada syndrome, whether it appears spontaneously or is induced by medication.
A different presentation, known as the Type 2 pattern, features a “saddleback” shape, where the ST-segment elevation is followed by a positive or biphasic T-wave. The Type 2 pattern is suggestive but insufficient for diagnosis alone, often requiring further testing to confirm the condition. Confirmation requires the Type 1 pattern to be present alongside clinical indicators, such as a history of fainting (syncope), documented ventricular fibrillation, or a family history of sudden cardiac death at a young age.
Conditions That Mimic Brugada Syndrome
A primary reason for misdiagnosis is the existence of numerous conditions that can create an ECG pattern identical to Brugada syndrome, known as “phenocopies.” These conditions are not genetic channelopathies but rather acquired states or structural heart issues that temporarily or chronically mimic the diagnostic Type 1 pattern. Recognizing these mimics is an essential step toward preventing a false-positive diagnosis and unnecessary intervention.
Common Phenocopies
One mimic is the early repolarization pattern, which is usually benign but can sometimes be confused with the Type 2 Brugada pattern, leading to clinical suspicion. Structural heart diseases, such as arrhythmogenic right ventricular cardiomyopathy (ARVC), can also present with ST-segment changes in the right precordial leads. While ARVC is a distinct disease involving structural changes, the overlap in electrical findings can complicate initial readings.
Inflammatory heart conditions, like acute myocarditis or pericarditis, may also produce a Brugada-like pattern, often as a temporary result of localized electrical changes. Similarly, mechanical factors, such as compression of the right ventricular outflow tract (RVOT) by a tumor or mass, have been documented to generate the characteristic ST-segment elevation.
Electrolyte imbalances within the body are another common source of Brugada-like ECG changes. Severe hyperkalemia, which is an excess of potassium in the blood, can alter the heart’s electrical current and lead to ST elevations resembling the syndrome. These electrical abnormalities typically disappear once electrolyte levels are corrected, distinguishing them from the persistent genetic defect of Brugada syndrome.
Factors Complicating Accurate Diagnosis
The transient and dynamic nature of Brugada syndrome itself presents a significant challenge to accurate diagnosis. For many individuals with the condition, the Type 1 pattern is not constantly visible on a standard ECG, often only appearing intermittently or under specific physiological stress. This variability means that a routine screening ECG may miss the diagnostic pattern entirely, resulting in a false-negative result.
External Triggers and Medications
Certain external triggers are well-documented to unmask the Type 1 pattern in people who have the genetic predisposition. Fever is one of the most common and potent triggers, causing a temporary appearance of the diagnostic pattern in otherwise asymptomatic individuals. This phenomenon can complicate the diagnosis during an acute illness, as the pattern may be misattributed to the fever itself or an infection.
A wide array of medications can also induce the Brugada ECG pattern, even in healthy hearts, or worsen it in those who already have the syndrome. These include certain antiarrhythmic drugs, specific psychotropic medications, and recreational substances like cocaine. A thorough review of the patient’s medication history is therefore required to determine if the ECG finding is drug-induced or a manifestation of the underlying syndrome.
Technical Errors
Technical errors during the recording of the ECG can create an appearance that falsely suggests the syndrome. Improper placement of the right precordial leads (V1 and V2) higher than the standard fourth intercostal space can artificially generate ST-segment elevation. Correcting the lead placement often resolves the apparent Brugada pattern, underscoring the importance of precise technique in the diagnostic process.
Specialized Tools for Confirmation
When the diagnosis is suspected but the resting ECG is inconclusive, specialized tools are used to confirm or rule out Brugada syndrome.
Pharmacologic Challenge Test
The most established tool is the pharmacologic challenge test, performed in a controlled hospital setting with continuous monitoring. This procedure involves the carefully administered intravenous infusion of a sodium channel blocking medication, such as ajmaline or flecainide. The goal of the drug challenge is to inhibit the sodium channels in the heart, intentionally mimicking the effect of the genetic defect. If the patient has Brugada syndrome, this stress test converts the non-diagnostic Type 2 or normal ECG into the definitive Type 1 coved pattern. This test is considered a powerful tool for unmasking the condition, particularly in patients who have experienced unexplained syncope or have a strong family history.
Genetic Testing and Specialist Consultation
Genetic testing analyzes the patient’s DNA for mutations in genes associated with the syndrome. The most commonly implicated gene is SCN5A, which codes for the primary sodium channel in the heart. While identifying a pathogenic mutation supports a diagnosis, a negative genetic test does not rule out Brugada syndrome, as many cases are caused by mutations in other genes or are currently unknown. Due to the complex nature of the diagnosis, which involves interpreting subtle ECG findings, ruling out mimics, and evaluating the results of challenge tests, consultation with a cardiac electrophysiologist is often required. These specialists have the expertise to synthesize all clinical, electrical, and genetic data to make a confident diagnosis, preventing both misdiagnosis and unnecessary treatment.