Cited by 616Cardiac electrophysiology and arrhythmiasIon channel regulation and functionCardiovascular Effects of Exercise

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ECG T-Wave Patterns in Genetically Distinct Forms of the Hereditary Long QT Syndrome

Moss, Arthur J., Zareba, Wojciech, Benhorin, Jesaia, Locati, Emanuela H., Hall, W. Jackson, Robinson, Jennifer L., Schwartz, Peter J., Towbin, Jeffrey A., Vincent, G. Michael, Lehmann, Michael H., Keating, Mark T., MacCluer, Jean W., Timothy, Katherine W.·1995·Circulation

DOI 10.1161/01.cir.92.10.2929

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Abstract

BACKGROUND: The long QT syndrome is an inherited disorder with prolonged ventricular repolarization and a propensity to ventricular tachyarrhythmias and sudden arrhythmic death. Recent linkage studies have demonstrated three separate loci for this disorder on chromosomes 3, 7, and 11, and specific mutated genes for long QT syndrome have been identified on two of these chromosomes. We investigated ECG T-wave patterns (phenotypes) in members of families linked to three genetically distinct forms of the long QT syndrome. METHODS AND RESULTS: Five quantitative ECG repolarization parameters, ie, four Bazett-corrected time intervals (QTonset-c, QTpeak-c, QTc, and Tduration-c, in milliseconds) and the absolute height of the T wave (Tamplitude, in millivolts), were measured in 153 members of six families with long QT syndrome linked to markers on chromosomes 3 (n = 47), 7 (n = 30), and 11 (n = 76). Genotypic data were used to define each family member as being affected or unaffected with long QT syndrome. Affected members of all six families had longer QT intervals (QTonset-c, QTpeak-c, or QTc) than unaffected family members (P < .01). Each of the three long QT syndrome genotypes was associated with somewhat distinctive ECG repolarization features. Among affected individuals, the QTonset-c was unusually prolonged in those individuals with mutations involving the cardiac sodium channel gene SCN5A on chromosome 3 (lead II QTonset-c [mean +/- SD]: chromosome 3, 341 +/- 42 ms; chromosome 7, 290 +/- 56 ms; chromosome 11, 243 +/- 73 ms; P < .001); Tamplitude was generally quite small in the chromosome 7 genotype (lead II Tamplitude, mV: chromosome 3, 0.36 +/- 0.14; chromosome 7, 0.13 +/- 0.07; chromosome 11, 0.37 +/- 0.17; P < .001); and Tduration was particularly long in the chromosome 11 genotype (lead II Tduration-c: chromosome 3, 187 +/- 33 ms; chromosome 7, 191 +/- 51 ms; chromosome 11, 262 +/- 65 ms; P < .001). Similar ECG findings were observed in leads aVF and V5. A considerable variability exists in the quantitative repolarization parameters associated with each genotype, with overlap in the T-wave patterns among the three genotypes. CONCLUSIONS: Three separate genetic loci for the long QT syndrome including mutations in two cardiac ionic channel genes were associated with different phenotypic T-wave patterns on the ECG. This study provides insight into the influence of genetic factors on ECG manifestations of ventricular repolarization.

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10.1161/circ.90.6.7994803 · DOI
10.1161/circ.82.2.2271025 · DOI
Bazett HC. An analysis of the time relations of electrocardiograms. Heart. 1920;7:353-367.

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Goldenberg, I., Barsheshet, A., & Huang, D. T.-C. (2023) · In clinical practice · doi:10.1007/978-3-031-41479-4_10
Long QT Syndrome and the Risk of Sudden Death in Adult Patients: An In-depth Analysis of Clinical Correlates and Prognostic Factors
López, D. E. S., Rojo, P. L. M., Jiménez, V. D., Ynostroza, S. I. M., Mendoza, A. A. S., & Sáenz, C. P. C. (2024) · International Journal of Medical Science and Clinical Research Studies · doi:10.47191/ijmscrs/v4-i03-15
Molecular Pathways and Animal Models of Arrhythmias
Stevens, T. L., Coles, S. A., Sturm, A. C., Hoover, C. A., Borzok, M. A., Mohler, P. J., & Refaey, M. E. (2024) · Advances in experimental medicine and biology · doi:10.1007/978-3-031-44087-8_67

Authors: Moss, A. J., Zareba, W., Benhorin, J., Locati, E. H., Hall, W. J., Robinson, J. L., Schwartz, P. J., Towbin, J. A., Vincent, G. M., Lehmann, M. H., Keating, M. T., MacCluer, J. W., & Timothy, K. W.
Affiliations: Texas Biomedical Research Institute (US)
From the Departments of Medicine (A.J.M., W.Z.), Community and Preventive Medicine (A.J.M., J.L.R.), and Biostatistics (W.J.H.), University of Rochester (NY) School of Medicine and Dentistry; Heiden Department of Cardiology, Bikur Cholim Hospital, Jerusalem, Israel (J.B.); Istituto di Clinica Medica Generale e Terapia Medica, University of Milan, Italy (E.H.L.); Section of Cardiology, Department of Internal Medicine, University of Pavia and Policlinico San Matteo IRCCS, Pavia, Italy (P.J.S.);...
ORCID: Moss, Arthur J.
Locati, Emanuela H.
Hall, W. Jackson
Robinson, Jennifer L.
Schwartz, Peter J.
Towbin, Jeffrey A.
Lehmann, Michael H.
Venue: Circulation
Publisher: Ovid Technologies (Wolters Kluwer Health)
Published: 1995-11-15
Volume: 92
Issue: 10
Pages: 2929-2934
ISSN: 0009-7322 (ISSN-L)
1524-4539
DOI: 10.1161/01.cir.92.10.2929
OpenAlex: W2085199612
Cited by: 616
References: 21
Citations by year: 2026: 2 · 2025: 8 · 2024: 16 · 2023: 11 · 2022: 6 · 2021: 13 · 2020: 11 · 2019: 5 · 2018: 12 · 2017: 20 · 2016: 18 · 2015: 16 · 2014: 13 · 2013: 18 · 2012: 28
FWCI: 19.53
Type: journal article
Language: en
Open access: closed
Locations: Circulation (publishedVersion)
PubMed (publishedVersion)
Funders: National Heart, Lung, and Blood Institute (R01 HL-51618, R01HL051618, R01HL-33843, R01HL033843)
Topics: Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Effects of Exercise
Keywords: QT interval, T-wave amplitude, T wave duration, SCN5A mutation, KCNQ1 mutation, chromosome 3, chromosome 7, chromosome 11, genotype-phenotype correlation, sudden cardiac death, ventricular repolarization, cardiac sodium channel
MeSH terms: Adult, Chromosome Mapping, Chromosomes, Human, Pair 11, Chromosomes, Human, Pair 3, Chromosomes, Human, Pair 7, Electrocardiography, Female, Genotype, Heart, Humans, Ion Channels, Genetic Linkage, Long QT Syndrome, Male, Mutation, Phenotype

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ECG T-Wave Patterns in Genetically Distinct Forms of the Hereditary Long QT Syndrome

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