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Brugada Syndrome (BS)
is a genetic cause of sudden cardiac arrest (SCA). In this
condition, SCA occurs due to the development of a fatal
arrhythmia (irregularity of the heart rhythm) arising from the
ventricles (lower chambers of the heart). This arrhythmia
prevents the ventricles from contracting effectively. Without
prompt defibrillation (electrical shock), death ensues within a
few minutes due to lack of blood flow to the body’s vital
approximately 30% of patients, SCA is the initial clinical
manifestation of BS. When the arrhythmia occurs, it tends to be
in the evening hours.
This is thought to be due to increased nocturnal
parasympathetic activity as part of the body’s natural circadian
with BS do not have structural heart disease on conventional
cardiac tests such as an echocardiogram, a stress test, or
cardiac catheterization. However, a standard electrocardiogram
(ECG) usually shows the characteristic abnormality: right bundle
branch block type morphology of the QRS complex with ST segment
elevation in the right precordial leads (V1 – V3;
Figure1). The differential diagnosis for the ECG pattern seen in
BS is extensive (Table 1) so not all patients with this sort of
ECG abnormality actually have the BS and thus will not be at
risk for SCA.
However because of this risk for sudden death, it is
important to identify and appropriately manage BS patients.
BS typically presents during adulthood.
Although most patients are in their 30’s to 40’s, BS has been
reported in patients as young as 2 years of age and as old as 84
years. Men are affected more commonly than women with a ratio of
8-9:1. The reason for this male preponderance is possibly
related to underlying differences in hormonal status. It is
estimated that BS is responsible for at least 4% of all sudden
deaths and at least 20% of all sudden deaths
occurring in patients without structural heart disease. The
syndrome occurs more commonly in Southeast Asians, with the
highest incidence occurring in the peoples of Northern Thailand.
Genetics and Pathophysiology
is a genetic disorder. In the inherited form, the mutant genes
are passed down from parents to offspring and the syndrome runs
in families. Since BS is an autosomal dominant disorder,
offspring of people with the mutant gene have a 50% chance of
inheriting it from their affected parent. A sporadic form is
also seen due to spontaneous mutations in the germ cells (ova or
sperm) of the patient’s parents affecting the segments of DNA
that code for the specific Brugada proteins.
date, the only gene linked with this condition, SCN5A, occurs on
chromosome 3. Only 18 to 30 percent of families with BS have
been found to have this mutant gene, making it likely that
additional genes, yet to be identified, are responsible for this
syndrome. The SCN5A gene codes for a defective sodium channel
protein. A normally functioning sodium channel is required for
the normal electrical activity of the heart. In patients with
BS, the defective sodium channel leads to development of chaotic
electrical activity which manifests itself as an arrhythmia. As
described above, this arrhythmia prevents proper ventricular
contraction and leads to sudden cardiac death. Genetic
counseling about BS is available through our center, as is the
commercially available test for SCN5A.
Since the normal electrical activity of the heart is altered,
patients with BS are also at increased risk for developing
non-lethal arrhythmias including an irregularly irregular rhythm
originating from the upper chambers of the heart called atrial
fibrillation (AF). Atrial fibrillation is observed clinically in
up to 20% of patients with BS. Other arrhythmias include AV
nodal reentrant tachycardia and Wolf-Parkinson-White syndrome.
While these arrhythmias tend not to be lethal they may lead to
complications in patients with BS such as inappropriate firing
from implanted cardioverter-defibrillator (ICD).
The ECG manifestations of Brugada syndrome are often
concealed, but can be unmasked by various clinical conditions
(such as fever), maneuvers or administration of certain drugs
(sodium channel blockers). These precipitating factors and
conditions cause changes in the electrical currents of the heart
leading to the abnormal ECG pattern typical of BS (Figure 2).
The diagnosis of BS is made by recording the electrical activity
of the patient’s heart. This is known as an ECG. Three ECG
patterns are recognized as being associated with BS (Figure 1).
Type 1 is the only type diagnostic of a Brugada pattern ECG.
Type 2 and 3 pattern ECGs are not diagnostic of Brugada and
require further evaluation. Diagnosis of BS is not always simple
and may require administration of medications or performing
specialized studies on the heart’s electrical system. Data from
these studies are combined with the medical history of the
patient or the patient’s family to determine if the patient: 1)
has BS and 2) the risk of SCA associated with the disorder.
The pharmacological approach to therapy is based on rebalancing
the abnormal electrical currents of the heart. Several
medications exist in the treatment of BS. However none of these
are associated with complete prevention of SCA. Therefore these
medications are reserved for controlling "electrical
storms" (incessant episodes of arrthymias) in BS.
Currently, ICDs are the only proven treatment for BS.
Furthermore, since SCA may be the initial manifestation of the
disease, it is critically important to identify patients who
many benefit from ICD implantation (Figure 3).
These patients include those with the type 1 ECG pattern
who have been successfully resuscitated from SCA or have had
unexplained syncope (loss of consciousness), seizures, or
nocturnal agonal respirations.
Antzelevitch C. Brugada P. Borggrefe M. et al:
Brugada syndrome: report of the second consensus conference:
endorsed by the Heart Rhythm Society and the European Heart
Rhythm Association. Circulation111;659-670, 2005.
The indications for ICD become less clear in asymptomatic
patients with the Brugada pattern on ECG, and unfortunately,
there is no consensus among physicians. One method for risk
stratifying asymptomatic patients is with an electrophysiology
study. Patients in whom a sustained ventricular arrhythmia (ventricular
fibrillation, polymorphic ventricular tachycardia, or
monomorphic ventricular tachycardia lasting >30
seconds) is inducible
are felt to be at high risk and may warrant ICD implantation.
However, the specificity of this test in this patient population
has been questioned. Thus, the management of asymptomatic
patients still remains to be definitively defined.