Brugada Syndome

 

Brugada Syndrome (BrS) is a rare arrhythmogenic cardiac channelopathy characterised by >0.2mV of ST segment elevation and negative T-wave in more than one anterior precordial leads (v1 v2, v3) and is associated with risk of sudden cardiac death resulting from lethal arrythmias (VF/VT). It is caused by mutation in cardio-myocyte voltage channels. Various mutations are implied resulting in BrS. Most common among them is the mutation in SCN5A, a sodium channel encoding gene. BrS has both familial (autosomal dominant) and sporadic variants.

Three Brugada ECG patterns (BEP) are seen in BrS. These BEP-Type1, Type 2 and Type 3 can be present in a same patient under different circumstances. But mostly patients present with any one of these patterns in their ECGs. Alternatively, a patient may have normal ECG and BEP is unmasked in certain conditions. BEP in ECG can be best brought out by placing the anterior precordial leads (v1 v2, v3) in 2nd or 3rd Intercostal spaces (high leads)

Most common among the provocative conditions that cause unmasking of BEP in ECG  of a BrS case  is fever. Other conditions/factors include acute illnesses and certain drugs. Recreational drugs like cannabis , cocaine and alcohol can also unmask BEP. These conditions can even precipitate a life-threatening arrhythmia in BrS patients. In patients with diagnosed or suspected Brugada syndrome, fevers should be aggressively treated and drugs that can provoke BEP should be avoided. (see http://www.brugadadrugs.org/avoid/).

A BEP in ECG is not exclusive for BrS.A Brugada Phenocopy(BrP) is a term used to describe a clinical condition in which the electrocardiographic (ECG) pattern mimics Brugada syndrome, but the cause is not a genetic mutation related to the syndrome itself. Other conditions that can cause a BrP in ECG are

1.    RBBB

2.    Pectus excavatum

3.    ARVD

4.    Early Repolarisation Syndrome

5.    Cocaine

6.    LVH

7.    Pericarditis

8.    Occlusion of LAD or Conus branch.

9.    Hyper Kalemia

10.  Hypothermia

Patients with BrP should be scrutinized to rule out above causes before considering the diagnosis or BrS.

BrS is usually considered as a diagnosis when BEP is present in ECG in following situations

1.    Asymptomatic pattern detected on health checkup

2.    VF/VT with post/pre resusitation ECG showing BEP

3.    Syncope caused probably by an arrythmia in a patient with BEP

4.    BEP unmasked by acute illness or drug consumption

5.    Nocturnal agonal respirations(sign of aborted arrythmia in sleep)

6.    Evaluation when family history of BrS is present

DIAGNOSIS
Only Type 1 BEP is diagnostic of BrS. Type 2 or type 3 pattern patients will have to undergo provocative drug testing with Sodium channel blockers(Flecainide, Ajmaline, procainamide, pilsicainide). The provocative testing should convert the pattern to Type 1 pattern. Along with this conversion, BrS is diagnosed if any one of the following is present

1.    Documented VF or VT

2.    Syncope of probable arrythmia cause

3.    Family history of SCD before age 45

4.    Family history of Brugada type 1 pattern

5.    Nocturnal agonal respirations.

Genetis testing is also valuable in evaluation of BrS.

Risk stratification in BrS is difficult. Two ECG findings can be helpful for identification of high-risk patients. A prominent R wave in lead aVR is a risk factor for arrhythmic events in BrS. This avR sign is defined as R wave >/= 0.3mV or R/q >/= 0.75 in lead avR. Another indicator for arrhythmia propensity is a S wave in lead I which is >/=0. 1mV and >/= 40msec.Electrophysiological testing can also be helpful in risk stratification.

TREATMENT

ICD implantation is warranted in patients with BrS with aborted SCD or spontaneous VT/VF or with a history of syncope. ICD implantation may be considered in patients with a type 1 ECG pattern and inducible VT/VF with two or less extra stimuli (programmed ventricular stimulation). Ablation in the epicardium of the anterior RV outflow tract can normalize the ECG and suppress VT. Ablation may be considered in patients with frequent ICD shocks. Quinidine can normalize the ECG and suppress the VT. Quinidine has been effective in patients with frequent or storms of VT/VF on ICD and may also be useful in patients who qualify for an ICD but either refuse or are otherwise contraindicated. In patients with VT storm secondary to Brugada syndrome, low-dose isoproterenol can also be effective in suppressing the arrhythmia.

 

References

GENERAL and TREATMENT

Braunwalds Heart Disease, A Textbook Of Cardiovascular Medicine, 11edition

DIAGNOSIS

J-Wave syndromes expert consensus conference report: Emerging concepts and gaps in knowledge: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5063270/

RISK STRATIFICATION IN BrS

Calò L, Giustetto C, Martino A, et al. A new electrocardiographic marker of sudden death in Brugada Syndrome: the S-wave in lead I. Journal of the American College of Cardiology. 2016;67(12):1427-1440. doi: 10.1016/j.jacc.2016.01.024.

aVR sign as a risk factor for life-threatening arrhythmic events in patients with Brugada syndrome DOI: 10.1016/j.hrthm.2007.04.017