Pathogenesis and management of Brugada Syndrome: Recent advances and protocol for umbrella reviews of meta-analyses in major arrhythmic events risk stratification

Brugada syndrome (BrS) is a primary electrical disease associated with life-threatening arrhythmias. It is estimated to cause at least 20% of sudden cardiac deaths (SCDs) in patients with normal cardiac anatomy. In this review paper, we discuss recent advances in complex BrS pathogenesis, diagnostics, and current standard approaches to major arrhythmic events (MAEs) risk stratification. Additionally, we describe a protocol for umbrella reviews to systematically investigate clinical, electrocardiographic, electrophysiological study, programmed ventricular stimulation, and genetic factors associated with BrS, and the risk of MAEs. Our evaluation will include MAEs such as sustained ventricular tachycardia, ventricular fibrillation, appropriate implantable cardioverter-defibrillator therapy, sudden cardiac arrest, and SCDs from previous meta-analytical studies. The protocol was written following the Preferred Reporting Items for Systematic review and Meta-Analysis Protocols (PRISMA-P) guidelines. We plan to extensively search PubMed, Embase, and Scopus databases for meta-analyses concerning risk-stratification in BrS. Data will be synthesized integratively with transparency and accuracy. Heterogeneity patterns across studies will be reported. The Joanna Briggs Institute (JBI) methodology, A MeaSurement Tool to Assess systematic Reviews 2 (AMSTAR 2), and the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) are planned to be applied for design and execution of our evidence-based research. To the best of our knowledge, these will be the first umbrella reviews to critically evaluate the current state of knowledge in BrS risk stratification for life-threatening ventricular arrhythmias, and will potentially contribute towards evidence-based guidance to enhance clinical decisions.