Role of Early Repolarization Pattern in Increasing Risk of Death

Cheng, Yun‐Jiu; Lin, Xuemei; Ji, Chengcheng; Chen, Xumiao; Liu, Lijuan; Tang, Kai; Wu, Shuizhu

doi:10.1161/jaha.116.003375

Cited by 38 publications

(43 citation statements)

References 40 publications

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“…It is prevalent in 2.3% to 29.3% of the population depending on race, age and gender category [2,3]. Several recent reports and our previous studies indicated that ERP was associated with increased risk for ventricular fibrillation (VF) and sudden cardiac death (SCD) in the general population and in patients with structural heart disease [2,[4][5][6]. The 2015 ESC Guidelines for the management of patients with ventricular arrhythmias defined early repolarization syndrome (ERS) as the presence of ERP with resuscitation from a documented episode of unexplained VF or polymorphic ventricular tachycardia (VT) [7].…”

Section: Introductionmentioning

confidence: 99%

A Heterozygous Missense hERG Mutation Associated with Early Repolarization Syndrome

Cheng¹,

Hao²,

Ji³

et al. 2018

Cell Physiol Biochem

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Background/Aims: Early repolarization syndrome (ERS) has been recently recognized as early repolarization pattern with idiopathic ventricular fibrillation. However, the genetic background of ERS has not been fully understood. Methods: A Chinese family with sudden cardiac death associated with ERS was investigated. Direct sequencing of ERS susceptibility genes was performed on the proband and family members. Whole-cell patch-clamp methods were used to characterize the mutant channel expressed in HEK 293 cells. Results: One missense mutation (p. K801T) was found in the hERG (KCNH2 gene) by the direct sequencing of candidate genes. Whole cell voltage clamp studies of the K801T mutation in HEK 293 cells demonstrated a 1.5-fold increase in maximum steady state current (37.2±7.3 vs 20.3±4.4 pA/pF) that occurred at a 20 mV more positive potential compared to the wild type channels. The voltage dependence of inactivation was significantly shifted in the positive voltage direction (WT -59.5±1.4 vs K801T -44.3±1.2 mV). Kinetic analysis revealed slower inactivation rates of K801T, but faster rates of activation and deactivation. The hERG channel blockers tested inhibited K801T-hERG channel in concentration response, and the potencies of these drugs can be rank-ordered as follows: quinidine> disopyramide> sotalol> flecainide. Conclusion: Our study indicated that the K801T mutation caused the gain of function of hERG channels that may account for the clinical phenotype of ERS. Quinidine and disopyramide could improve the function of K801T-hERG mutant channel, and may be therapeutic options for patients with the K801T hERG mutation.

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Section: Introductionmentioning

confidence: 99%

A Heterozygous Missense hERG Mutation Associated with Early Repolarization Syndrome

Cheng¹,

Hao²,

Ji³

et al. 2018

Cell Physiol Biochem

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“…The critical role of the ER pattern in initiating ventricular fibrillation has been supported by observations of a consistent and marked J-wave accentuation preceding the onset of arrhythmia (1,10) and by electrophysiology (EP) mapping data that suggested an association between the origin of ectopy that initiated VF and the location of repolarization abnormalities (1). Meta-analysis on 16 studies involving 334524 subjects suggests that the ER pattern is associated with an increased risk for sudden cardiac arrest, cardiac death, and death from any cause (11). …”

Section: Introductionmentioning

confidence: 99%

The Electrophysiological Substrate of Early Repolarization Syndrome

Zhang

Hocini

Ström³

et al. 2017

JACC: Clinical Electrophysiology

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Background The early repolarization (ER) pattern is a common ECG finding. Recent studies established a definitive clinical association between ER and fatal ventricular arrhythmias. However, the arrhythmogenic substrate of ER in the intact human heart has not been characterized. Objectives To map the epicardial electrophysiological (EP) substrate in ER syndrome patients using noninvasive Electrocardiographic Imaging (ECGI), and to characterize substrate properties that support arrhythmogenicity. Methods Twenty-nine ER syndrome patients were enrolled, 17 of which had a malignant syndrome. Characteristics of the abnormal EP substrate were analyzed using data recorded during sinus rhythm. The EP mapping data were analyzed for electrogram morphology, conduction and repolarization. Seven normal subjects provided control data. Results The abnormal EP substrate in ER syndrome patients has the following properties: (1) Abnormal epicardial electrograms characterized by presence of J-waves in localized regions; (2) Absence of conduction abnormalities, including delayed activation, conduction block, or fractionated electrograms; (3) Marked abbreviation of ventricular repolarization in areas with J-waves. The action potential duration (APD) was significantly shorter than normal (196±19 vs. 235±21 ms, p<0.05). Shortening of APD occurred heterogeneously, leading to steep repolarization gradients compared to normal control (45±17 vs.7±5 ms/cm, p<0.05). Premature ventricular contractions (PVCs) were recorded in 2 patients. The PVC sites of origin were closely related to the abnormal EP substrate with J-waves and steep repolarization gradients. Conclusions Early Repolarization is associated with steep repolarization gradients caused by localized shortening of APD. Results suggest association of PVC initiation sites with areas of repolarization abnormalities. Conduction abnormalities were not observed.

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“…Since then, the term “ER” has been ambiguously used to describe either of these ECG signs, perhaps due to the confusing inclusion of a “J” in both terms. Although these findings can theoretically coexist in some individuals, they should be considered separately .…”

Section: Early Repolarizationmentioning

confidence: 99%

“…In an attempt to summarize the large amount of data published since the first reports, Cheng et al . recently conducted a meta‐analysis of 16 studies and 334,524 subjects to examine the link between ER and the risk of SCD.…”

Section: Early Repolarizationmentioning

confidence: 99%

The new kids on the block of arrhythmogenic disorders: Short QT syndrome and early repolarization

Mazzanti

Underwood

Nevelev

et al. 2017

Cardiovasc electrophysiol

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Short QT syndrome (SQTS) is one of the rarest inheritable cardiac channelopathies, characterized by an accelerated cardiac repolarization, which is also the substrate for the development of life-threatening ventricular arrhythmias. Up to this date, fewer than 200 SQTS cases have been reported in the literature worldwide. Patients with SQTS may experience a cardiac arrest as early as in the neonatal period or as late as 80 years old. The cumulative probability of experiencing a cardiac arrest by the fifth decade of life approaches 40%, highlighting the importance of early recognition and management. SQTS is an autosomal dominant disease with five identified causative genes, including three that encode for potassium channels (KCNH2, KCNQ1, and KCNJ2) and two that encode for subunits of the L-type calcium channels (CACNA1C and CACNB2). The term "early repolarization" (ER) has long been used to refer to a heterogeneous group of specific QRS-T junction patterns that are commonly found on the electrocardiograms of young healthy subjects. In the last decade, it has been suggested that in some individuals, the presence of ER may be associated with an increased risk of sudden cardiac death, and thus the term "early repolarization syndrome" (ERS) has progressively entered into use. Up to this point, however, whether ER constitutes a true primary arrhythmic disorder or whether it is simply a predisposing substrate that facilitates arrhythmias in the presence of other triggers remains an unresolved issue. In this review paper, we aim to integrate the current literature on SQTS and ERS. For each, we will describe the key steps that first led to the identification of the syndrome before moving into a discussion of our current understanding of each entity, including the epidemiology, genetics, diagnosis, clinical manifestations, and management.

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Role of Early Repolarization Pattern in Increasing Risk of Death

Cited by 38 publications

References 40 publications

A Heterozygous Missense hERG Mutation Associated with Early Repolarization Syndrome

A Heterozygous Missense hERG Mutation Associated with Early Repolarization Syndrome

The Electrophysiological Substrate of Early Repolarization Syndrome

The new kids on the block of arrhythmogenic disorders: Short QT syndrome and early repolarization

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