Functional Significance of KCNH2 (HERG) K897T Polymorphism for Cardiac Repolarization Assessed by Analysis of T‐Wave Morphology

Linna, Eeva; Perkiömäki, Juha S.; Karsikas, Mari; Seppänen, Tapio; Savolainen, Markku J.; Kesäniemi, Y. Antero; Mäkikallio, Timo H.; Huikuri, Heikki V.

doi:10.1111/j.1542-474x.2006.00083.x

Cited by 11 publications

(11 citation statements)

References 20 publications

(63 reference statements)

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“…The two SNPs that appear to have the strongest connection to (patho)physiological phenotypes are rs1805123 in exon 11 and rs1036145 in intron 2. The minor allele in rs1805123 results in residue 897 changing from lysine to threonine (K897T) and has been identified in genome-wide association studies as a significant determinant of QT interval duration (126,374,397,444,496). The minor allele in SNP rs1036145 is significantly correlated with expression of the KCNH2-1c isoform, which is correlated with development of schizophrenia (279).…”

Section: A Kcnh2 Genementioning

confidence: 97%

hERG K⁺Channels: Structure, Function, and Clinical Significance

Vandenberg

Perry

Perrin

et al. 2012

Physiological Reviews

605

773

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The human ether-a-go-go related gene (hERG) encodes the pore-forming subunit of the rapid component of the delayed rectifier K(+) channel, Kv11.1, which are expressed in the heart, various brain regions, smooth muscle cells, endocrine cells, and a wide range of tumor cell lines. However, it is the role that Kv11.1 channels play in the heart that has been best characterized, for two main reasons. First, it is the gene product involved in chromosome 7-associated long QT syndrome (LQTS), an inherited disorder associated with a markedly increased risk of ventricular arrhythmias and sudden cardiac death. Second, blockade of Kv11.1, by a wide range of prescription medications, causes drug-induced QT prolongation with an increase in risk of sudden cardiac arrest. In the first part of this review, the properties of Kv11.1 channels, including biogenesis, trafficking, gating, and pharmacology are discussed, while the second part focuses on the pathophysiology of Kv11.1 channels.

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Section: A Kcnh2 Genementioning

confidence: 97%

hERG K⁺Channels: Structure, Function, and Clinical Significance

Vandenberg

Perry

Perrin

et al. 2012

Physiological Reviews

605

773

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“…This polymorphism influences cardiac repolarization and has functional significance for cardiac electrical properties. Subjects with a less common genotype had smaller spQRSTa values which reflects desynchronization between depolarization and repolarization and is associated with an increased risk of cardiac mortality [63]. …”

Section: The Spqrsta: Epidemiological Datamentioning

confidence: 99%

The Spatial QRS-T Angle: Implications in Clinical Practice

Voulgari

Pagoni²,

Tesfaye³

et al. 2013

CCR

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The ventricular gradient (VG) as a concept was conceived in the 1930s and its calculation yielded information that was not otherwise obtainable. The VG was not utilized by clinicians at large because it was not easy to understand and its computation time-consuming. The contemporary spatial QRS-T angle is based on the concept of the VG and defined as its mathematical and physiological integral. Its current major clinical use is to assess the cardiac primary repolarization abnormalities in 3-dimensional spatial vectorial plans which are normally untraced in the presence of secondary electrophysiological activity in a 2-dimensional routine electrocardiogram (ECG). Currently the calculation of the spatial QRS-T angle can be easily computed on the basis of a classical ECG and contributes to localization of arrhythmogenic areas in the heart by assessing overall and local heterogeneity of the myocardial ventricular action potention duration. Recent population-based studies suggest that the spatial QRS-T angle is a dominant ECG predictor of future cardiovascular events and death and it is superior to more conventional ECG parameters. Its assessment warrants consideration for intensified primary and secondary cardiovascular prevention efforts and should be included in everyday clinical practice. This review addresses the nature and diagnostic potential of the spatial QRS-T angle. The main focus is its role in ECG assessment of dispersion of repolarization, a key factor in arrythmogeneity.

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“…For each ECG, the digital signal of one beat of each lead was used. Several descriptors of T-wave and QRS complex morphology were automatically calculated from the 12-lead ECGs, using a custom-made software application [15,25]. The maximum amplitude of the T-wave is defined as the difference between the peak of the T-wave and the baseline.…”

Section: Methodsmentioning

confidence: 99%

“…The QT interval was also measured in every lead of the surface ECG and QT dispersion was calculated using the difference between the maximum and minimum of the QT interval in any of the leads. The ECGs were scanned and digitised using UN-SCAN-IT Graph Digitising System Version 6.0 (Silk Scientific, Orem, UT, USA) [15,25]. For each ECG, the digital signal of one beat of each lead was used.…”

Section: Methodsmentioning

confidence: 99%

Effects of controlled hypoglycaemia on cardiac repolarisation in patients with type 1 diabetes

et al. 2007

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Aims/hypothesis Nocturnal hypoglycaemia may contribute to sudden death in diabetic patients. However, it is not well known why hypoglycaemia makes these patients prone to death. Methods We assessed the effects of controlled hypoglycaemia on cardiac repolarisation using novel electrocardiographic descriptors of T-wave and QRS complex morphology in 16 type 1 diabetic patients and eight healthy counterparts. Several electrocardiographic variables characterising repolarisation were analysed from digitised 12-lead electrocardiograms during a euglycaemic and a hypoglycaemic clamp. Results Hypoglycaemia did not result in significant changes either in the QT interval corrected for heart rate by the nomogram method or in QT dispersion. However, the morphology of the T-wave changed significantly during hypoglycaemia. The T-wave amplitude and area in precordial leads decreased significantly in both groups (p<0.05 to p<0.001). The spatial QRS-T angle (total cosine R to T) (p<0.05) and the height and the width of the T-wave loop (p<0.05 and p<0.01, respectively) were also reduced in the diabetic patients. The changes in the repolarisation parameters did not exhibit any significant association with changes in catecholamine levels or in heart rate variability in either group. Conclusions/interpretation Hypoglycaemia results in distinct alterations in cardiac repolarisation, which may increase the vulnerability to arrhythmic events.

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Functional Significance of KCNH2 (HERG) K897T Polymorphism for Cardiac Repolarization Assessed by Analysis of T‐Wave Morphology

Cited by 11 publications

References 20 publications

hERG K⁺Channels: Structure, Function, and Clinical Significance

hERG K⁺Channels: Structure, Function, and Clinical Significance

The Spatial QRS-T Angle: Implications in Clinical Practice

Effects of controlled hypoglycaemia on cardiac repolarisation in patients with type 1 diabetes

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Functional Significance of KCNH2 (HERG) K897T Polymorphism for Cardiac Repolarization Assessed by Analysis of T‐Wave Morphology

Cited by 11 publications

References 20 publications

hERG K+Channels: Structure, Function, and Clinical Significance

hERG K+Channels: Structure, Function, and Clinical Significance

The Spatial QRS-T Angle: Implications in Clinical Practice

Effects of controlled hypoglycaemia on cardiac repolarisation in patients with type 1 diabetes

Contact Info

Product

Resources

About

hERG K⁺Channels: Structure, Function, and Clinical Significance

hERG K⁺Channels: Structure, Function, and Clinical Significance