Address for correspondence:
Pattara Rattanawong, MD
Department of Cardiovascular Medicine
Mayo Clinic
5777 East Mayo Boulevard
Phoenix, AZ, USA, 85054
Phone: 808-859-3848
Email: Rattanawong.pattara@mayo.edu
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.
Keywords: Drug challenge testing, Brugada syndrome, Sodium
channel blocker