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Genetic Architecture, Pathophysiology, and Clinical Management of Brugada Syndrome

  • John R. Giudicessi
  • Michael J. AckermanEmail author
Chapter

Abstract

Brugada syndrome (BrS) is a genetically complex and heterogeneous disorder characterized by ST-segment elevation in the right precordial leads and an increased risk of syncope and sudden cardiac death in the setting of an otherwise structurally normal heart. Over the last several years, advances at both the bench and the bedside have begun to question existing paradigms surrounding the genetic basis and pathophysiology of BrS as well as usher in novel approaches to the risk stratification and treatment of patients with this potentially fatal disorder. In this chapter, we examine the rapidly evolving understanding of the pathophysiological mechanism(s) underlying BrS, ongoing efforts to reappraise the genetic architecture of BrS, and advances in risk stratification and therapeutic approaches that are redefining how patients with BrS are managed clinically.

Keywords

Arrhythmia Brugada syndrome Genetics Genetic testing Sudden cardiac death 

Abbreviations

ACC

American College of Cardiology

AHA

American Heart Association

BrS

Brugada syndrome

ClinGen

Clinical Genome Resource

EHRA

European Heart Rhythm Association

EPS

Electrophysiology study

ESC

European Society of Cardiology

ExAC

Exome Aggregation Consortium

gnomAD

Genome Aggregation Database

GUS

Gene of uncertain significance

GWAS

Genome-Wide Association Study

HRS

Heart Rhythm Society

ICD

Implantable cardioverter-defibrillator

PVC

Premature ventricular contraction

RVOT

Right ventricular outflow tract

SCD

Sudden cardiac death

VF

Ventricular fibrillation

VT

Ventricular tachycardia

VUS

Variant of uncertain significance

Notes

Funding Sources

This work was supported by the Mayo Clinic Windland Smith Rice Sudden Comprehensive Sudden Cardiac Death Program (to Dr. Ackerman). Dr. Giudicessi thanks the Mayo Clinic Cardiovascular Diseases Fellowship and Clinician Investigator Training Programs for fostering an outstanding environment for physician-scientist training.

Conflict of Interest Disclosures

Dr. Ackerman is a consultant for Audentes Therapeutics, Boston Scientific, Gilead Sciences, Invitae, Medtronic, MyoKardia, and St. Jude Medical. From 2004 to 2016, M.J.A. and Mayo Clinic received sales-based royalties from Transgenomic for their FAMILION-LQTS and FAMILION-CPVT genetic tests. M.J.A. and Mayo Clinic have an equity/royalty relationship (without remuneration so far) with AliveCor, Blue Ox Health, and StemoniX. However, none of these entities participated in this study. Dr. Giudicessi declares no conflicts.

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Copyright information

© Springer Nature Switzerland AG 2020

Authors and Affiliations

  1. 1.Department of Cardiovascular MedicineMayo ClinicRochesterUSA
  2. 2.Departments of Cardiovascular Medicine, Pediatric and Adolescent Medicine, and Molecular Pharmacology and Experimental TherapeuticsMayo Clinic Genetic Heart Rhythm Clinic and the Windland Smith Rice Sudden Death Genomics LaboratoryRochesterUSA

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