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Circulation. 1995;92:2929-2934

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(Circulation. 1995;92:2929-2934.)
© 1995 American Heart Association, Inc.

Articles

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

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

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.); Department of Pediatric Cardiology, Baylor College of Medicine, Houston, Tex (J.A.T.); Cardiology Division, Eccles Program in Human Molecular Biology and Medicine, Department of Human Genetics, and Howard Hughes Medical Institute of the University of Utah Health Sciences Center (M.T.K.), Salt Lake City; Departments of Medicine (G.M.V., K.W.T.) and Internal Medicine (G.M.V.), University of Utah School of Medicine, Salt Lake City; Arrhythmia Center, Sinai Hospital, Detroit, Mich (M.H.L.); and Department of Genetics, Southwest Foundation for Biomedical Research, San Antonio, Tex (J.W.M.).

Correspondence to Arthur J. Moss, MD, Heart Research Follow-up Program, Box 653, University of Rochester Medical Center, Rochester, NY 14642. E-mail heartajm@heart.heart.rochester.edu.

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.


Key Words: electrocardiography • genetics • intervals • arrhythmia




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