Impact of clinical and genetic findings on the management of young patients with Brugada syndrome

Heart Rhythm. 2016 Jun;13(6):1274-82. doi: 10.1016/j.hrthm.2016.02.013. Epub 2016 Feb 24.

Abstract

Background: Brugada syndrome (BrS) is an arrhythmogenic disease associated with sudden cardiac death (SCD) that seldom manifests or is recognized in childhood.

Objectives: The objectives of this study were to describe the clinical presentation of pediatric BrS to identify prognostic factors for risk stratification and to propose a data-based approach management.

Methods: We studied 106 patients younger than 19 years at diagnosis of BrS enrolled from 16 European hospitals.

Results: At diagnosis, BrS was spontaneous (n = 36, 34%) or drug-induced (n = 70, 66%). The mean age was 11.1 ± 5.7 years, and most patients were asymptomatic (family screening, (n = 67, 63%; incidental, n = 13, 12%), while 15 (14%) experienced syncope, 6(6%) aborted SCD or symptomatic ventricular tachycardia, and 5 (5%) other symptoms. During follow-up (median 54 months), 10 (9%) patients had life-threatening arrhythmias (LTA), including 3 (3%) deaths. Six (6%) experienced syncope and 4 (4%) supraventricular tachycardia. Fever triggered 27% of LTA events. An implantable cardioverter-defibrillator was implanted in 22 (21%), with major adverse events in 41%. Of the 11 (10%) patients treated with hydroquinidine, 8 remained asymptomatic. Genetic testing was performed in 75 (71%) patients, and SCN5A rare variants were identified in 58 (55%); 15 of 32 tested probands (47%) were genotype positive. Nine of 10 patients with LTA underwent genetic testing, and all were genotype positive, whereas the 17 SCN5A-negative patients remained asymptomatic. Spontaneous Brugada type 1 electrocardiographic (ECG) pattern (P = .005) and symptoms at diagnosis (P = .001) were predictors of LTA. Time to the first LTA event was shorter in patients with both symptoms at diagnosis and spontaneous Brugada type 1 ECG pattern (P = .006).

Conclusion: Spontaneous Brugada type 1 ECG pattern and symptoms at diagnosis are predictors of LTA events in the young affected by BrS. The management of BrS should become age-specific, and prevention of SCD may involve genetic testing and aggressive use of antipyretics and quinidine, with risk-specific consideration for the implantable cardioverter-defibrillator.

Keywords: Arrhythmia; Brugada syndrome; Genetics; Pediatrics; Quinidine.

Publication types

  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Asymptomatic Diseases / epidemiology
  • Brugada Syndrome* / diagnosis
  • Brugada Syndrome* / genetics
  • Brugada Syndrome* / physiopathology
  • Brugada Syndrome* / therapy
  • Child
  • Death, Sudden, Cardiac / etiology
  • Death, Sudden, Cardiac / prevention & control
  • Defibrillators, Implantable
  • Electric Countershock* / instrumentation
  • Electric Countershock* / methods
  • Electrocardiography / methods
  • Female
  • Humans
  • Male
  • NAV1.5 Voltage-Gated Sodium Channel / genetics*
  • Prognosis
  • Risk Assessment
  • Syncope / etiology
  • Syncope / prevention & control
  • Tachycardia, Ventricular / diagnosis
  • Tachycardia, Ventricular / etiology
  • Tachycardia, Ventricular / prevention & control

Substances

  • NAV1.5 Voltage-Gated Sodium Channel
  • SCN5A protein, human