Heritability of Early Repolarization

Abstract

Background-Early repolarization (ER), defined by J-point elevation in 12-lead ECG, was recently associated with increased risk for idiopathic ventricular fibrillation and cardiovascular mortality. The determinants of ER are unknown. We investigated its heritability in a large, family-based cohort. Methods and Results-The study sample comprised 1877 individuals from 505 white nuclear families representative of the British general population. Standard 12-lead ECGs were evaluated for the presence of ER, defined as J-point elevation of Ն0.1 mV in at least 2 adjacent inferior (II, III, and aVF) or anterolateral (I, aVL, and V 4 through V 6 ) leads. Narrow sense heritability estimates were computed adjusting for age, age 2 , and sex. The prevalence of ER was 7.7% (nϭ145) in the whole cohort, 5.9% (nϭ56) in parents, and 9.6% (nϭ89)

A Clinical Approach to Early Repolarization

“…A study involving 505 Caucasian nuclear families reported that individuals with ≥1 parent with ER had a 2.5-fold increased incidence of demonstrating the ER pattern. 50 Familial transmission appeared more frequent when the mother was affected (3.8-fold versus 1.8-fold, P=0.1). Potential explanations for unequal transmission include transmission through mitochondrial DNA, effects mediated via sex chromosomes, and parental imprinting of autosomal genes.…”

“…25,50 In 2 large population-based cohorts, 25 siblings of individuals with ER had an increased unadjusted odds of ER (odds ratio, 2.22; P=0.047). A study involving 505 Caucasian nuclear families reported that individuals with ≥1 parent with ER had a 2.5-fold increased incidence of demonstrating the ER pattern.…”

The Prevalence and Significance of the Early Repolarization Pattern in Sudden Arrhythmic Death Syndrome Families

“…Although this definition differs slightly from a recent consensus document, 21 it is in keeping with that used by Tikkanen et al 17 when first demonstrating the prognostic benefit of ST-segment gradient. Similar criteria, described previously, 6 were used for the control population. J-point amplitude was categorized in 0.1 mV increments (ie, 0.10-0.19 mV; 0.20-0.29 mV, etc) and considered high amplitude if ≥0.2 mV.…”

“…3 In addition, there is increasing evidence for the role of ER as a risk factor for arrhythmic events in the context of other inherited arrhythmia syndromes. 4,5 Several studies have suggested the ER pattern is a heritable phenotype 6,7 and variants in genes encoding cardiac ion channels [8][9][10] have been identified in individuals and families with ERS.…”

Letter by Hayashi et al Regarding Article, “Heritability of Early Repolarization: A Population-Based Study”

“…

We read with much interest the article published by Reinhard et al 1 The article described a high rate of heritability of early repolarization (ER) in a general population. Early repolarization was characterized by ECG morphological features of the QRS complex (ie, notching, slurring, or both).

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