Brugada syndrome

y

rSR', downsloping ST elevation V1 - V2.

Brugada syndrome is an established cause of SCD in patients without structural abnormalities. Syncope, ventricular dysrhthmia, or SCD or arrest may be the presenting symptom, although detection of the characteristic right precordial ST-segment elevation on ECG can be potentially lifesaving intervention.

In 1992, EPS Pedro and Joseph Brugada reported 8 cases of syncope and SCD in patients with structurally normal hearts who had ST-segment elevation on ECG in the right precordial leads V1 to V3. This primary abnormality is known as Brugada syndrome, and is estimated to be responsible for 4% of all SCD and 20% of sudden deaths in patients with structurally normal hearts.

Epidemiology:

  • AD genetic d/o

  • Adulthood during 30s and 40s; mean age at Dx is 40 years and mean age of SCD is 41 years.

  • Although less common cause of SCD in children and infants.

  • Prevalence 1 to 5 per 10,000.

  • Commonly seen in Thailand, Phillipines, and Europe.

  • Men > women 8:1 and may be associated with higher levels of testosterone.

Clinic Presentation:

  • SCD preceded by polymorphic VTy

  • Supraventricular dysrhythmias occur in up to 20% of patients, with AF being a concomitant rhythm disorder in 11% to 14% of patients.

  • Other commonly associated conduction abnormalities are first-degree AV block with PR interval of >200 ms, RBBB, and SSS.

  • SCD implicates a vagal mechanism initiated by bradycardia because death usually occurs between midnight and 6 a.m.

  • Nocturnal agonal respiration, or erratic gasping breaths during sleep, also can be a presenting sign of Brugada syndrome and may be a manifestation of ventricular dysrhythmias that spontaneously self-terminate.

  • The predilection of SCD at night is though to be due to hormonal imbalance or an imbalance of the sympathetic and parasympathetic nervous system.

Genetics:

  • AD, genetic mutation

  • 12 genes have been linked to Brugada syndrome.

  • 15% to 30% express a mutation in the gene that encodes for the alpha subunit of the cardiac sodium channel, SCN5A, located on chromosome 3p21-24.

  • This sodium channelopathy causes a decrease in influx of sodium into cardiac cells that shortens the normal action potential of myocytes.

  • Genetic mutations are present in only 25% of patients, implying that further heterogeneity has yet to be discovered.

  • Genetic testing is only to be done, if definitive diagnosis of Brugada syndrome has been made; genetic testing of family members is recommended if a genotype has been associated with the proband.

Pathophysiology:

  • ST-segment elevation in patients with Brugada syndrome is thought to be caused by alterations in transmembrane ion currents of the cardiac action potential, which appear to affect the right ventricular endocardium differently than the RV epicardium

  • The ST segment electrically represents the time between ventricular depolarization and repolarization, and normally is isoelectric. Changes in repolarization in patients with Brugada syndrome can lead to a transmural voltage gradient, reexcitation, extrasystolic beats, and an electrophysiologic phenomenon known as phase 2 reentry that can lead to PVCs, polymorphic VT, and VT.

Diagnosis:

  • European society of cardiology identified 3 repolarization patterns associated with Brugada syndrome, all in the right precordial leads V1 to V3.

  • The three pattern show two distinctive patterns of ST-segment elevation: type 1 and type 2.

  • The 2013 expert consensus recommendations on Brugada syndrome diagnosis required ST segment elevation in one precordial lead.

  • Type 1 ST-segment elevation:

    • J wave amplitude of 2 mm or greater

    • Negative T wave, and little isoelectric segment in between.

    • This pattern has a distinct coved shape ST-segment elevation and is diagnostic of Brugada syndrome.

  • Type 2 ST-segment elevation:

    • Saddleback or downsloping ST-segment and T-wave morphology, with the ST-segment descending to the isoelectric line and rising to a biphasic or positive T wave.

    • This pattern may suggest an underlying pathology of Brugada syndrome, but is not diagnostic unless the patient displays a type 1 pattern when administered a class Ia or Ic antiarrhythmic agent.

  • The same patient may display a normal, type 1, or type 2 ECG over his or her lifetime. If a type 1 pattern of ST-segment elevation has not been documented and a Brugada syndrome is suspected, or, if a type 2 pattern is documented, perform an IV drug challenge with a class Ia or Ic antiarrhythmic to unmask an underlying type 1 pattern. However, a sodium channel is not warranted in patients with a type 1 pattern since the pattern is definitive for Brugada syndrome.

  • The drug infusion challenge should be performed with continuous ECG monitoring in a facility capbable of ACLS because the challenge may induce ventricular dysrhythmias.

  • When recording a 12 lead ECG during a drug challenge, or when attempting to rule out Brugada syndrome, place the right precordial leads at the level of 2nd intercostal space. not the 4th. This position anatomically traverses the right ventricular outflow tract, which has a greater density of potassium channels and can better display early repolarization, thereby improving the sensitivity of identifying a Brugada pattern.

Triggers:

  • Fever

  • Consumption of large meals

  • Cocaine

  • Alcohol toxicity

DDx:

  • Several benign and pathophysiologic conditions that cause ST-segment elevation at the right precordial leads must be ruled out.

    • MI, ischemia

    • Hyerkalemia, hyokalemia, hypercalcemia

    • Early repolarization syndrome in young athletes.

    • Arrythmogenci right ventricular dysplasia

    • CM

    • Prinzmetal angina

    • LVH

    • PE

    • DMD

    • Compression of right ventricular outflow tract via tumor or hemopericardium, pectus excavatum, dissecting aortic aneurysm, and atypical LBBB.

      • Echocardiography, stress echo, and cardiac MRI is used to exclude structural cardiac defects.

Guidelines for IV drug challenge:

Key drug categories in Brugada syndrome

To be avoided:

  • Antiarrhythmics: ajmaline, ethacizin, flecainide, lappaconitine hydrobromide, pilsicainide, procainamide, propafenone

  • Psychotropic: amitryptiline, clomipramine, desipramine, lithium, loxapine, notriptyline, oxcarbazepine, trifluoperazine

  • Anesthetic/analgesic: bupivacaine, procaine, propofol

  • Other substances: acetylcholine, alcohol toxicity, cannabis, cocaine, ergonovine

To be preferably avoided

  • Antiarrhythmics amiodarone, cibenzoline, disopyramide, lidocaine, propanolol, vernakalant, verapamil

  • Psychotropic: bupropion, doxepin, fluoxetine, fluvoxamine, imipramine, maprotiline, paroxetine, perphenazine, phenytoin, thioridazine

Potential antiarrhythmic drugs

  • Bepridil

  • Isoproterenol

  • Isoprenaline

  • Orciprenaline

  • Qunidine

  • Cilostazol

Diagnostic drugs

  • Ajmaline

  • Flecainide

  • Pilsicainide

  • Procainamide