‘Brugada Syndrome’ :   The first case-report from India .                  -    Satish Kumar*, A.K. Singh*, S. K. Singh*, D. C. Mathur*,                     A. K. Pandey†.                                              * Bokaro General Hospital , Bokaro Steel City .                     † Heritage Hospital , Varanasi .

Abstract            In 1992, Brugada brothers- Josep & Pedro- of Barcelona published a series of 8 cases of sudden death, RBBB pattern and ST-elevation in V1 - V3 in apparently healthy individuals1. This 'Brugada Syndrome' is basically an ‘Ion-Channel Defect’ due to a mutation in sodium channel (SCN5A) and has an Autosomal Dominant inheritance with variable _expression2. Being a pro- arrhythmic condition, this accounts for 4-12% of unexpected sudden deaths worldwide and is the commonest cause of Sudden Cardiac Death in individuals aged less than 50 years in South East Asia . During the last decade there has been an exponential increase in the number of patients recognized all over the world. However, no documented case has been reported from India , so far.            We present a case of a young male who presented with history of recurrent syncope with a typical Brugada ECG. His 24-hour Holter record revealed paroxysms of polymorphic NSVT. As the condition was unresponsive to drug therapy, the patient was later referred to a higher center for Electro-Physiological Study where the diagnosis was confirmed and he was implanted an AICD with good results.            This syndrome is one of the examples of the fascinating abilities of the 100 years old electrocardiography in discovering new clinical entities in Cardiology.   Key Words:  Brugada Syndrome, Sudden Cardiac Death, Ion-Channel Defect, AICD.

Address for correspondence:-

Dr. Satish Kumar, [ L - 2288 ]

Qr. No.- 1134 , Sector 4 /C; Bokaro Steel City ; Jharkhand , India . PIN - 827004 .

( e-mail:bko_drsatish@sancharnet.in )

Case History

In May 2002 , a 29 yr. old Hindu male was referred to us for Pacemaker Implantation with the diagnosis of - ‘Antero-Septal Myocardial Infarction ĉ Bifascicular Block ĉ recurrent Syncope. (?) Intermittent Complete Heart Block.’ However, the patient never had angina and no risk factors for CAD were known. According to him he experienced multiple episodes of paroxysmal palpitation, some culminating in fainting attacks during last 6 months. In between the episodes he remained totally symptom-free. There had never been a documented A-V dissociation.

During his childhood he was on some anticonvulsants for seizures for few years which were stopped in 1993 as no seizure recurred for years while on treatment. He was on no any medication in recent past. He had no addictions.

The family history was interesting. His 32 year old, apparently healthy uncle had died suddenly 5 years ago without any obvious reason while traveling in a train. It was suspected that he was poisoned by a fellow traveler but this could not be confirmed and the cause of his death remained a mystery as no ECG was available nor any autopsy was done. Other members of his family apparently enjoyed good health except his mother who is diabetic.               **                                                                                           

On admission, his 12 -lead ECG showed LAHB with cRBBB, ST-coving in V _{2 - 3} and normal PR & QT intervals. [Fig.– 1 ] Patient’s blood chemistry, including cardiac enzymes and serum electrolytes were all within normal levels. The ECHO was essentially normal - no RWMA, chamber size & other measurements normal, and no evidence of any LV Aneurism to explain the ECG abnormalities.                                                                                                                                                                                                           

Expecting some bradyarrhythmic event as the reason for his syncopal attacks, a 24 -Hr. Holter monitoring was done. But, to our surprise, it revealed few runs of symptomatic polymorphic NSVT following ‘R-on-T’ phenomena [Fig.–2]. No A-V dissociation or bradycardia occurred. QTc remained normal.

It was at this time that we reviewed the ECG which clearly showed -‘Brugada Pattern’ !  

So, the patient was put on Amiodarone 200 mg od after a loading dose with no response on events & symptoms. Later, Metoprolol 25 mg bd was added to it but no appreciable result could be obtained. Patient continued to have fainting spells due to Ventricular Tachyarrhythmias, fortunately ill-sustained.  

As such he was referred for Electro-Physiolocal Study (EPS) which could elicit inducible VT amenable to electro-cardioversion. Later, he was implanted an Automated Implantable Cardioverter-Difibrillator (AICD) with very good results. He has been largely asymptomatic after the procedure.

Discussion

Sudden Cardiac Death (SCD), which refers to any natural death from cardiac causes occurring within one hour of the onset of symptoms, is most often due to CAD ( 80 %) followed by the Cardiomyopathies -  (DCM or HCM).

Among the less common causes are the Congenital Heart Diseases, Valvular Diseases, RV dysplasia and Primary electrical & genetic ion-channel abnormalities. Examples are accessory pathways (WPW & LGL Syndromes), Cong. Long QT Syndromes and Lenegre-Lev Disease. Brugada Syndrome is a new entrant in this category, described only during the last decade. In 1992 , Brugada brothers - Pedro and Josep of Barcelona published a series of 8 cases of sudden death in apparently healthy individuals with characteristic ECGs .¹ Since then, a number of patients have been recognized all over the world to have similar ECG changes. This syndrome may account for some 4 - 12 % of unexpected sudden deaths and up to 50 % of all sudden death in patients with an apparently normal heart. It is the commonest cause of SCD in individuals aged less than 50 years in South East Asia . However, to the best of our search, no documented case has been reported from India , till date.

Basically, Brugada Syndrome is a clinico-electrocardiographic diagnosis based on the history of syncopal or aborted SCD episodes in patients with structurally normal hearts with a characteristic electrocardiographic pattern: The ECG shows ‘epsilon-shaped’ ST-segment elevation in the precordial leads V ₁ to V ₃ with the morphology of the QRS complex resembling right bundle branch block. This pattern of RBBB has also been called J-point elevation.

The episodes of syncope and sudden death (aborted or not) are caused by fast polymorphic VT, "Torsade de Pointes" or VF. These arrhythmias appear with no warning. There is no dyselectrolytaemia or prolongation of the QT-interval. Also, there is no preceding acceleration in the heart rate as is the case of cathecolamine-dependent polymorphic VT.

Surprisingly, at times, these unique ECG changes may be altogether absent!  In such cases, certain Provocative Tests may elicit the ST elevation. However they must be done in an ICU setup with facilities for CPR because in 0.5 % of tests the patient may develop VF. Classically, IV Ajmaline has been used for the purpose but as it is no longer available, Flecainide or Procainamide are being used. Flecainide is given IV in Europe ( 2 mg/Kg body weight over 10 minutes), but 200 mg orally may be given. Patient must be monitored for 8 hours because of the long half-life. The  test is considered positive if an additional 1 mm ST segment coved elevation appears in leads V ₁ _ ₃ (essentially in V 2 , and either V 1 or V3 -usually both).

Aetiology : This syndrome is genetically determined. Approximately 60 % of patients with (aborted) sudden death with the typical ECG have a family history of sudden death, or have family members with the same ECG changes. There are also sporadic cases who are probably the patients with a de novo mutation in the family. The pattern of transmission is ‘Autosomal Dominant’ with a definite male predominance. The disease is associated with a mutation in sodium channel gene (SCN 5 A on Chromosome 3 ) .²

The early theory was that the syndrome reflected an increase in the Ito channel (governing the potassium current in phase 1 of the ECG). In fact, the Ito current is only increased relative to the sodium current, because the sodium channel closes prematurely.

It is important to note that Na-channel mutations are also associated with congenital LQTS type- 3 and PCCD (Lenegre-Lev Disease) .⁵ Kindred were described that showed overlapping phe-notypes, so that at different times an individual may express more than one phenotype.

The occurrence of these overlapping syndromes has important clinical implications. For example, Flecainide which has been suggested as a potential treatment for LQT 3 may precipitate serious arrhythmias in patients with the LQT 3 / Bruguda overlap.

Prognosis :  This syndrome has a very poor prognosis when left untreated: 2 / 3 rd. of the cases are diagnosed only after an episode of syncope or resuscitation from near-sudden death. Unfortunately, prognosis of asymptomatic individuals with typical ECG is also poor. In a study, recurrent arrhythmic events occurred in 34 % of symptomatic and 27 % of asymptomatic patients on 34 month follow-up.

The 5 year mortality due to sudden cardiac death in Brugada Syndrome*

                                                                                        *After: Circulation 1998;97[5]:457-60

These data are of extreme importance for the delineation of treatment policies of these patients. Because the antiarrhythmic drugs (Amiodarone or Beta-blockers) do not protect against SCD, the only available treatment is the implantable cardioverter-defibrillator.

Work-up : Every patient, symptomatic or not, having the classic Brugada ECG at baseline should undergo an Electro-Physiological Study (EPS) and if found +ve for inducible arrhythmia, need AICD. Symptomatic patients or those with strong family history of SCD who get ECG changes on provocation also need EPS. ECGs can normalize over time. A completely normal ECG in one moment doesn’t mean it will always be normal. If the ECG ever becomes abnormal, like on Holter-monitoring, then follow-up with provocative tests and then EPS is required.

Asymptomatic patients who have a normal basal ECG have 0 % events in follow-up, so far. So, EPS is not warranted in these patients. However, in asymptomatic persons if the basal ECG is abnormal, then EPS should follow. Among them 2 / 3 is non-inducible & if so, nothing is required as the event rate is extremely low. But, if there is inducible arrhythmia, events are frequent to warrant an AICD.

References:

1. Brugada P, Brugada J. ‘Right Bundle Branch Block, Persistent ST Segment Elevation and Sudden Cardiac Death: A Distinct Clinical and Electrocardiographic Syndrome’. J Am Coll Cardiol 1992;20:1391-6.

2. Priori SG, Barhanin J, Hauer RN, et al. ‘Genetic and molecular basis of cardiac arrhythmias: impact on clinical management - Part III’. Circulation 1999;99:674-81.

3. Benhorin J, Taub R, Goldmit M, et al. Effects of flecainide in patients with new SCN 5 A mutation: mutation-specific therapy for long-QT syndrome? Circulation 2000 ; 101 : 1698 - 1706 .

4. Bezzina CR, Groenewegen WA , Lam J, et al Double heterozygosity for mutations in SCN 5 A associated with severe cardiac conduction disturbances. Program and abstracts of the North American Society of Pacing and Electrophysiology 21 Annual Scientific Sessions; May 17 - 20 , 2000 ; Washington , DC . PACE. 2000 ; 23 (part II): 604 . Abstract 205 .

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