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

Abstract

Background-The early repolarization (ER) pattern is associated with sudden death and has been shown to be heritable. Its significance when identified in families affected by sudden arrhythmic death syndrome (SADS) remains unclear. Methods and Results-We analyzed 12-lead ECGs of 401 first-degree relatives of individuals who had died from SADS.The prevalence of ER patterns was compared with family-clustered controls. ER was more common in SADS family members than in controls (21% versus 8%; odds ratio: 5.14; 95% confidence interval, 3.37-7.84) independent of the presence of a familial cardiac diagnosis. Both ascending and horizontal ER patterns were more common. In addition, ER was investigated for associations with findings from ajmaline provocation (n=332), exercise ECG (n=304), and signalaveraged ECG (n=118) when performed. ER was associated with a trend toward late depolarization, in general was suppressed with exercise and was unaffected by ajmaline. Inferior and horizontal patterns were, however, more likely to persist during exercise. Augmentation of ER with ajmaline was rare. Conclusions-The ER pattern is more common in SADS family members than controls adjusted in particular for relatedness.The increased prevalence is irrespective of ER subtype and the presence of other inherited arrhythmia syndromes. ER may therefore represent an underlying heritable arrhythmia syndrome or risk factor for sudden death in the context of other cardiac pathology. The differing response of ER subtypes to exercise and ajmaline provocation suggests underlying mechanisms of both abnormal repolarization and depolarization. (Circ Arrhythm Electrophysiol. 2016;9:e003960.

KCND3 potassium channel gene variant confers susceptibility to electrocardiographic early repolarization pattern

“…Studies among first-degree relatives of patients with sudden arrhythmic death syndrome show that ERP is more prevalent in family members than in controls, indicating that ERP is an important potentially inheritable proarrhythmic trait (18,19). Moreover, in family studies, the heritability estimate for the presence of ERP was h 2 = 0.49 (20).…”

European Heart Rhythm Association (EHRA)/Heart Rhythm Society (HRS)/Asia Pacific Heart Rhythm Society (APHRS)/Latin American Heart Rhythm Society (LAHRS) Expert Consensus Statement on the state of genetic testing for cardiac diseases

“…293 It is over-represented in families of UCA survivors 294 and autopsy negative SCD families. 295,296 There has not yet been a consensus curation for ERS. SCN5A variants with loss-of-function (determined by patch clamping expression studies) have been identified in 2-10% of patients with ERS, the patients showed signs of conduction slowing, supporting a depolarization phenotype.…”

The narrow-sense and common single nucleotide polymorphism heritability of early repolarization

“…Previous work has shown that first-degree relatives of autopsy negative SCD victims have increased prevalence of ER with both rapidly ascending and horizontal/descending ST-segment morphologies, when compared to matched nuclear families [27]. A recent study demonstrated higher prevalence of ER in survivors of unexplained cardiac arrest (UCA) who had first-degree relatives with the ER pattern [28].…”