The Utility of Drug Challenge Testing in Brugada Syndrome: a Systematic
Review and Meta-analysis
Abstract
Introduction: Brugada syndrome is associated with ventricular arrhythmia
leading to sudden cardiac death. Risk stratification is challenging, as
major arrhythmic events (MAE) are rare. We assessed the utility of drug
challenge testing in Brugada syndrome by a systematic review and
meta-analysis. Methods and results: We comprehensively searched the
databases of MEDLINE and EMBASE from inception to May 2019. Included
studies compared the incidence of MAE between spontaneous and drug
challenge induced Type-1. Data were combined using the random-effects,
generic inverse variance method, to calculate pooled incidence and odds
ratio (OR). Mixed-effects Poisson regression was used to calculated
incidence rate ratio (IRR). Eighteen studies from 2006 to 2018 were
included (4,099 patients, mean follow-up 4.5 years). Pooled annual
incidences of MAE in spontaneous, drug challenge induced (regardless of
symptoms), asymptomatic drug challenge induced, and symptomatic drug
challenge induced Type-1 were 23.8 (95% confidence interval [CI]:
19.8-27.8), 6.5 (95% CI: 3.9-9.1), 2.1 (95% CI: -0.3-4.4), and 19.6
(95% CI: 9.9-29.3) per 1,000 person-years respectively. The incidence
of MAE between symptomatic drug challenge induced and asymptomatic
spontaneous Type-1 was not statistically different (IRR=1.0, 95%CI:
0.6-1.7). The presence of ventricular tachyarrhythmia during drug
challenge testing was a predictor of MAE (OR=3.73, 95% CI: 1.77-7.86,
p=0.001). Conclusions: The incidence of MAE in drug challenge induced
Type-1 in asymptomatic patients is low. The incidence of MAE between
symptomatic drug challenge induced and asymptomatic spontaneous Type-1
was similar. Ventricular tachyarrhythmia during drug challenge testing
could be a useful risk marker for MAE in Brugada syndrome.