Brugada syndrome

From Ask Dr Wiki

Contents 1 Background 2 Characteristics 3 Brugada EKG 4 Diagnosis 5 Sodium Challenge 6 Arrhythmias 7 Risk Statification 8 Treatment 9 References

Background

• Brugada syndrome is associated with high risk of sudden death in young adults, and occasionally in children and infants.
• Introduced as a new clinical entity by Pedro and Josep Brugada in 1992

Characteristics

• Characterized by a coved-type ST-segment elevation in the right precordial leads
• The Brugada ECG is often concealed, but can be unmasked or modulated by a number of drugs and pathophysiological states including sodium channel blockers, a febrile state, vagotonic agents, tricyclic antidepressants, as well as cocaine and Propranolol intoxication.
• Average age at the time of initial diagnosis or sudden death is 40 ± 22, with the youngest patient diagnosed at 2 days of age and the oldest at 84 years.
• The prevalence of the Brugada syndrome is estimated at 1–5 per 10,000 inhabitants worldwide. The frequency is lower in western countries and higher (≥5 per 10,000) in Southeast Asia.
• Genetics

1. SCN5A is a gene that encodes the alpha sodium unit of the cardiac sodium channel. Mutations in SCN5A account for about 15-30% of Brugada syndrome cases. A negative genetic test for SCN5A does not exclude that SCN5A is causing the clinical syndrome because the genetic tests do not evaluate for mutations in promotors, cryptic splicing mutations, or gross rearrangements in the protein product.
2. Glycerol-3-phosphate dehydrogenase (GPD1L) is associated with progressive conduction disease and low sensitivity to procainamide resulting from decreased Isodium current. It has a relatively good prognosis.
3. CACNA1C (alpha subunit of L-type cardiac calcium channel) and CACNB2b (beta subunit of L-type cardiac calcium channel) is associated with a shortened QT interval and a combinatin Brugada/Short QT interval syndrome.

Brugada EKG

1. Type 1 ST segment elevation is diagnostic of Brugada syndrome and is characterized by a coved ST-segment elevation ≥2 mm (0.2 mV) followed by a negative T wave.
2. Type 2 ST-segment elevation has a saddleback appearance with a high take-off ST-segment elevation of ≥2 mm followed by a trough displaying ≥1 mm ST elevation followed by either a positive or biphasic T wave.
3. Type 3 ST-segment elevation has either a saddleback or coved appearance with an ST-segment elevation of <1 mm.

Diagnosis

• Diagnosed when a Type 1 ST-segment elevation is observed in more than one right precordial lead (V1-V3), in the presence or absence of sodium channel blocking agent, and in conjunction with one or more of the following:

1. Family history of SCD (<45 years old)
2. Documented VF
3. Polymorphic ventricular tachycardia
4. Coved-type ECGs in family members
5. Inducibility of VT with programmed electrical stimulation (PES)
6. Syncope
7. Nocturnal agonal respiration

• Diagnosis is also considered positive when a Type 2 (saddleback pattern) or Type 3 ST-segment elevation is observed in more than one right precordial lead under baseline conditions and can be converted to the diagnostic Type 1 pattern occurs upon exposure to sodium channel blocker.

Sodium Challenge

• Drugs that can be used
  • Ajmaline 1 mg/kg/5 min IV
  • Flecainide 2 mg/kg/10 min IV or 400 mg PO
  • Procainamide 10 mg/kg/10 min IV
  • Pilsicainide 1 mg/kg/10 min IV
• The sodium challenge should be terminated when

1. Diagnostic Type 1 ST-segment elevation or Brugada ECG, develops
2. ST segment in Type 2 increases by ≥2 mm
3. Premature ventricular beats or other arrhythmias develop
4. QRS widens to ≥130% of baseline

Arrhythmias

1. Polymorphic VT resembling a rapid Torsade de Pointes (TdP)
2. Monomorphic VT is observed infrequently
3. VT/VF often terminates spontaneously in patients with the Brugada syndrome which may explain why patients wake up at night after episodes of agonal respiration caused by the arrhythmia.

Risk Statification

• Patients with syncope and an abnormal Type 1 ECG are at higher risk
• Asymptomatic patients at risk can be identified
  • Presence of spontaneous Type 1 ST-segment elevation
  • Characteristics of the S wave
  • Presence of late potentials
  • Inducibility of VT/VF using PES.

Treatment

• Aborted sudden death are at high risk for recurrence and should receive an ICD
• VT storm has been successfully treated with Isoproterenol. The mechanism is thought to be augmenting the cardiac L type channel.
• Asymptomatic patients require risk stratification and clinical judegement to help guide therapy
• Quinidine (class IA sodium channel blocker) blocks the Ito current and is proven to suppress spontaneous VF
• Cilostazol (phosphodiesterase III inhibitor that increases inward L type calcium channel current and reported to suppress spontaneous VF
• Bepridil suppress spontaneous VF probably through blocking Ito current
• Medical therapy alone with the above agents is currently not evaluated in randomized trials and should not be used as loan therapy.

References

1. Brugada Syndrome. Charles Antzelevitch, PH.D. PACE 2006; 29:1130–1159
2. Brugada P, Brugada J. Right bundle branch block, persistent ST segment elevation and sudden cardiac death: A distinct clinical and electrocardiographic syndrome: A multicenter report. J Am Coll Cardiol 1992; 20:1391–1396.
3. Antzelevitch C, Brugada P, Brugada J, Brugada R, Shimizu W, Gussak I, Perez Riera AR. Brugada syndrome. A decade of progress. Circ Res 2002; 91:1114–1119. 3. Wilde AA, Antzelevitch C, Borggrefe M, et al. Proposed diagnostic criteria for the Brugada syndrome: Consensus report. Eur Heart J 2002; 23:1648–1654.
4. Wilde AA, Antzelevitch C, Borggrefe M, et al. Proposed diagnostic criteria for the Brugada syndrome: Consensus report. Circulation 2002; 106:2514–2519.
5. 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. Circulation 2005; 111:659–670.
6. Antzelevitch C, Brugada P, Borggrefe M, et al. Brugada syndrome:Report of the second consensus conference. Heart Rhythm 2005; 2:429–440.

Image:Brugada.pdf