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Genetics, Molecular Biology, and Emerging Concepts of Early Repolarization Syndrome

  • Charles Antzelevitch
  • Gregory Dendramis
Chapter

Abstract

Early repolarization pattern (ERP) has traditionally been regarded as benign and is often encountered in apparently healthy individuals. In the absence of organic heart disease and when associated with ventricular tachycardia (VT) or fibrillation (VF), ERP is referred to as early repolarization syndrome (ERS) and is considered to be one of the J wave syndromes (JWS). To date, ERS has been associated with variants in seven different genes but a large number of variants remain in “genetic purgatory.” In ERS, an outward shift in the balance of current during the early phase of the left ventricular (LV) epicardial action potential (AP) secondary to genetic defects in either inward or outward currents is thought to lead to accentuation of the Ito-mediated action potential (AP) notch in ventricular epicardium but not endocardium, giving rise to a J wave in the ECG, particularly in the inferior LV. Loss of the AP dome at some epicardial sites but not others creates an epicardial dispersion of repolarization giving rise to phase 2 reentrant extrasystole. Loss of the epicardial AP dome also creates a transmural dispersion of repolarization giving rise to a vulnerable window across the ventricular wall which when captured by the closely coupled phase 2 reentrant extrasystole can induce VT/VF. Recent consensus statements and guidelines provide recommendations for therapy of ERS. The most effective therapy for the prevention of SCD in high-risk ERS patients is an implantable cardioverter defibrillator (ICD). The pharmacologic approach to therapy involves inhibition of Ito, augmentation of ICa or slowing of inactivation of INa. Experimental evidence has been advanced showing an ameliorative effect of radiofrequency ablation of the inferior LV epicardium; however clinical data are lacking at this time.

Keywords

Sudden cardiac death Cardiac electrophysiology  J wave syndrome  Cardiac arrhythmias  Sudden cardiac death 

Abbreviations and Acronyms

AP

action potential

ECG

electrocardiogram

EG

electrogram

ERS

early repolarization syndrome

BrS

Brugada syndrome

JWS

J wave syndromes

LV

left ventricle

P2R

phase-2-reentry

RFA

radiofrequency ablation

RVOT

right ventricular outflow tract

VF

ventricular fibrillation

VT

ventricular tachycardia

Notes

Funding

We acknowledge support from NIH-NHLBI Grant #HL47678, the W.W. Smith Charitable Trust Grant #1820 and from the Martha and Wistar Morris Fund.

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Copyright information

© Springer Nature Switzerland AG 2020

Authors and Affiliations

  • Charles Antzelevitch
    • 1
    • 2
    • 3
  • Gregory Dendramis
    • 4
  1. 1.Department of Cardiovascular ResearchLankenau Institute for Medical ResearchWynnewoodUSA
  2. 2.Lankenau Heart InstituteWynnewoodUSA
  3. 3.Sidney Kimmel Medical School, Thomas Jefferson UniversityPhiladelphiaUSA
  4. 4.Cardiovascular DivisionPietro Cosma HospitalPadovaItaly

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