The Utility of Sodium Channel Provocation in Unexplained Cardiac Arrest Survivors and Electrocardiographic Predictors of Ventricular Fibrillation Recurrence

Circ Arrhythm Electrophysiol. 2022 Dec;15(12):e011263. doi: 10.1161/CIRCEP.122.011263. Epub 2022 Nov 28.

Abstract

Background: The implications of a drug-induced type 1 Brugada ECG pattern following sodium channel blocker provocation (SCBP) are not fully understood.

Methods: Baseline clinical and ECG data were obtained from consecutive unexplained cardiac arrest survivors undergoing SCBP at 3 centers. A further 15 SCBP positive (SCBP+) unexplained cardiac arrest survivors were recruited from 3 additional centers to explore ventricular fibrillation recurrence.

Results: A total of 121 consecutive unexplained cardiac arrest survivors underwent SCBP. The yield of the drug-induced type 1 Brugada ECG pattern was 17%. A baseline type 2/3 Brugada pattern (T2/3BP) (adjusted odds ratio, 19.36 [2.74-136.61]; P=0.003) and PR interval (odds ratio, 1.03 [1.01-1.05] per ms; P=0.017) were independent predictors of SCBP+ response. A pathogenic SCN5A variant was identified in 36% of the SCBP+ group versus 0% in the SCBP- group (P<0.001). Amongst SCBP+ patients, a spontaneous type 1 Brugada pattern was identified in 19% during follow up and in 24% a type 1 Brugada pattern was identified in a relative. Prior syncope (adjusted hazard ratio, 3.83 [1.36-10.78]; P=0.011) and the presence of global early repolarization (hazard ratio, 7.91 [3.22-19.44]; P<0.001) were independent predictors of 5-year ventricular fibrillation recurrence. There was a nonsignificant trend toward greater 5-year ventricular fibrillation recurrence in the SCBP- group (23/95 [24%] versus 3/34 [9%]; P=0.055).

Conclusions: The yield of the drug-induced type 1 Brugada ECG pattern in consecutive unexplained cardiac arrest survivors undergoing SCBP is 17%. A baseline T2/3BP and PR interval were independent predictors of the drug-induced type 1 Brugada ECG pattern. Greater heritability of BrS phenotype in this group was evidenced by a greater prevalence of pathogenic SCN5A variants and relatives with a type 1 Brugada pattern. A history of prior syncope and the presence of global early repolarization were independent predictors of ventricular fibrillation recurrence.

Keywords: Brugada Syndrome; early repolarization; sodium channel provocation; sudden death; ventricular fibrillation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arrhythmias, Cardiac
  • Brugada Syndrome* / diagnosis
  • Death, Sudden, Cardiac / epidemiology
  • Electrocardiography
  • Heart Arrest* / diagnosis
  • Heart Arrest* / epidemiology
  • Heart Arrest* / etiology
  • Humans
  • Prevalence
  • Sodium Channel Blockers
  • Survivors
  • Syncope
  • Ventricular Fibrillation / diagnosis
  • Ventricular Fibrillation / genetics

Substances

  • Sodium Channel Blockers