Brugada Syndrome By Dr. Rabe3 Alansi Yemen

Case 1

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40 year old man presented to the emergency department after losing consciousness while driving his car. He had felt nauseous and light headed before managing to slow down and stop. A witness who stopped to help found him slumped unconscious over the steering wheel, and he regained consciousness a few seconds later.

On arrival in hospital he was fully alert although he felt light headed and He has been investigated,the noncardic causes of syncop are excluded & the cardic enzymes & echo are normal BUT; (ECG) shows changes were identical to those seen in the ECGs performed three years previously ,how to corrolate ECG findings to clinical picture, what is next step for evaluation of this case ??

The same Pt. underwent check up investigations before 3 years, he had no symptoms & the heart & other systems by clincal exam.were nomal.& imaging studies including echo show no abnormalites, though ECG shows specific changes ; does it has

Al-KWAIT University Hospital Sanaa yemen

why Brugada syndrome has recently attracted great interest ??

becau seFirst, of : The disease takes the lives, in many First

instaces as a first event, of previously healthy indiviuals in their forties,during their most productive years. Second ,once thought to be very rare, the BS is now recognized world wide & has a high prevalance in certain parts of world.

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Definition

Brugada syndrome (BS) is : an inherited form of cardiac arrhythmia and sudden death presenting with : a typical electrocardiographic pattern of ST segment elevation in leadsV1 to V3, and displaying a right bundle branch block QRS morphology

It is most frequently diagnosed in YOUNG MALES (8:1 ratio of males:females) of Asian origin.

History Of Brugada syndrome Interestingly, the natives knew the problem for many decades. In the Northeast of Thailand, this form of death was known as Lai Tai (death during sleep). The indigenous believe that the young men died during sleep because widow ghosts came to take them away. Many young men actually dress still as women to go to sleep at night - with the hope that it would mislead the widow ghost. In Philippines the phenomenon was known as Bangungut (scream followed by sudden death during sleep)

The first patient with this syndrome was seen in In Japan was known as Pokkuri (unexpected sudden death 1986. at night).. The first paper including 8 patients was published in 1992 Since then, there has been an exponential increase in the number of patients recognized all

The Incidence

the Brugada syndrome has progressed from being a rare disease to one that is second only to automobile accidents as a cause of death among young adults in some countries. Brugada syndrome is affecting 5/10 000 of the general population, But ,is estimated to be responsible for at least 4% of all sudden deaths and at least 20% of sudden deaths in patients with structurally normal hearts

Clinical Characteristics PT. presents with :

The syncope and cardiac arrest that typically occurring in the 3ed and 4th decade of life, and usually at rest or during sleep. The manifestations of BS are due to : syncopal episodes of polymorphic ventricular When the episodes terminate tachycardia-ventricular fibrilations attacks. When the episodes are sustained

sudden death

Thus ,these manifestations can range widely: at one end of the spectrum we have asymptomatic individuals & at other end those who die suddenly.

Diagnostic Criteria

@ Update 2005 @

Brugada syndrome is definitively diagnosed when :  Type 1 ECG (elevation of the J wave 2 mm with (a negative T wave )and ST segment that is coved type and gradually descending) in more than one right precordial lead (V1-V3)*, with or without administration of a sodium channel blocker) and  A. and/or B. below:  A at least one of the following findings: Documented ventricular fibrillation Self-terminating polymorphic ventricular tachycardia A family Hx of sudden cardiac death Coved-type ECGs in family members Electrophysiologic inducibility Syncope or nocturnal agonal respiration  B An SCN5A mutation

The ECG manifestations of the Brugada syndrome

The ECG manifestations of the ,Brugada syndrome

The dynamic ECG manifestations of ,the Brugada syndrome

coved (type 1).

‘saddle back

The ECG manifestations of Brugada syndrome are often concealed & dynamic but can be unmasked or modulated by:  sodium channel blockers, blockers  a febrile state,  vagotonic agents,  hyperkalemia, hypokalemia, hypercalcemia,  and alcohol and cocaine toxicity

The use of Drug challenge to unmask BS

‘saddle back (type 2)

1, 2, 3, 4 min during i.v. infusion of 50 mg ajmaline.

unmasked & becomes coved (type 1).

Circadian pattern of VF episodes in patients with BS

 VF and sudden death in Brugada syndrome usually occur at rest and at night.  Circadian variation of sympathovagal balance, hormones, and other metabolic factors are likely to contribute to this circadian pattern. We can notice ventricular episodes increase at mid night due to Circadian pattern of BS

Genetic Factors Underlying Brugada Syndrome 

The first and only gene to be linked to Brugada syndrome is SCN5A, the gene that encodes for the subunit of the cardiac sodium channel gene.



SCN5A mutations account for 18% to 30% of Brugada syndrome cases

• Genetic testing is recommended, however, to • Support the clinical diagnosis, • For early detection of relatives at potential risk,

Risk Stratification and Electrophysiological (EP) study Electrophysiological (EP) study: This test may be performed to determine the inducibility of arrhythmias in B S. The predictive value of the EP study is still debated.

Risk Stratification 1. Patients have a relatively high risk for sudden arrhythmic death, even in the absence of a history of cardiac arrest: 8.2% experienced sudden death 2.Individuals with a spontaneously abnormal type 1 ECG carried a 7.7-fold higher risk of developing an arrhythmic event during a lifetime as compared with individuals in whom the ECG diagnostic of Brugada syndrome was

Risk Stratification 3. Programmed electrical stimulation that induces a sustainedventricular arrhythmia is the strongest marker of risk, associated with an 8-fold higher risk of (aborted) sudden death than in noninducible patients. 4. Male gender is another risk factor for sudden death. Men had a 5.5-fold higher risk of sudden death than did women. 5. Familial forms of the disease are not associated with a worse prognosis than are sporadic cases because a positive

Therapeutic Recommendations for Brugada Syndrome Currently, an ICD is the only proven effective treatment for the disease

Treatment with pharmacological agents is usually unsuccessful

The pharmacological approach The only agent on the US market is quinidine. Class 1C antiarrhythmic drugs (eg, flecainide and propafenone) and class IA agents (eg,procainamide) are contraindicated Antiarrhythmic agents such as amiodarone and B-blockers have been shown to be ineffective.

The pharmacological approach The most recent drug, cilostazol, which normalizes the ST segment most likely by augmenting the calcium current (ICa), as well as by reducing I to secondary to an increase in heart rate. An experimental agent, tedisamil, with potent action to block I to among other outward currents has been suggested as a therapeutic candidate

Recommendations for ICD implantation : Symptomatic patients  1 Symptomatic patients displaying the type 1 BrugadaECG (either spontaneously or after sodium channel blockade) + presenting with aborted sudden death. 2 Similar patients + presenting related symptoms such as syncope, seizure, or nocturnal agonal respiration also

Pt. should undergo ICD implantati on

Recommendations for ICD implantation Asymptomatic: patients 1 Asymptomatic patients displaying a type 1 ECG + a family history of sudden cardiac death 2 Asymptomatic patients who develop a type 1 ECG only after sodium channel blockade + no family history

should undergo EPS If inducible, then the patient should receive an ICD. should be closely followed up

The Prognosis This syndrome has a very poor prognosis when left untreated. Untreated Brugada’s syndrome is associated with a 10% mortality per year with up to 40% of patients experiencing arrhythmias in the future.  prognosis of asymptomatic individuals : One third of patients having suffered from syncopal episodes develops a new episode of polymorphic ventricular tachycardia within 2 years.