(Circulation. 2000;102:2849.)
© 2000 American Heart Association, Inc.
Clinical Investigation and Reports |
Spectrum of ST-T–Wave Patterns and Repolarization Parameters in Congenital Long-QT Syndrome
ECG Findings Identify Genotypes
From LDS Hospital (L.Z., K.W.T., G.M.V., J.F., L.C.G., F.Y.), Salt Lake City, Utah; University of Utah School of Medicine (G.M.V., S.J.C., J.S., I.S, F.Y., M.T.K.), Salt Lake City; University of Michigan (M.H.L.), Ann Arbor; Molecular Cardiology (S.G.P.), Maugeri Foundation, Pavia, Italy; Bikur Cholim Hospital (J.B., A.M.), Jerusalem, Israel; University of Rochester School of Medicine and Dentistry (A.J.M., J.L.R., W.Z.), Rochester, NY; Policlinico S. Matteo IRCCS (P.J.S., C.N.), Milan, Italy; Cleveland Clinic Foundation (Q.W.), Cleveland, Ohio; and Baylor College of Medicine (J.A.T.), Houston, Tex.
Correspondence to G. Michael Vincent, MD, Department of Internal Medicine, LDS Hospital, Physician Office Building, Suite 130, 324 10th Ave, Salt Lake City, UT 84103. E-mail ldgvince{at}ihc.com
Background—Congenital long-QT syndrome (LQTS) is caused by mutations of genes encoding the slow component of the delayed rectifier current (LQT1, LQT5), the rapid component of the delayed rectifier current (LQT2, LQT6), or the Na+ current (LQT3), resulting in ST-T–wave abnormalities on the ECG. This study evaluated the spectrum of ST-T–wave patterns and repolarization parameters by genotype and determined whether genotype could be identified by ECG.
Methods and Results—ECGs of 284 gene carriers were studied to determine ST-T–wave patterns, and repolarization parameters were quantified. Genotypes were identified by individual ECG versus family-grouped ECG analysis in separate studies using ECGs of 146 gene carriers from 29 families and 233 members of 127 families undergoing molecular genotyping, respectively. Ten typical ST-T patterns (4 LQT1, 4 LQT2, and 2 LQT3) were present in 88% of LQT1 and LQT2 carriers and in 65% of LQT3 carriers. Repolarization parameters also differed by genotype. A combination of quantified repolarization parameters identified genotype with sensitivity/specificity of 85%/70% for LQT1, 83%/94% for LQT2, and 47%/63% for LQT3. Typical patterns in family-grouped ECGs best identified the genotype, being correct in 56 of 56 (21 LQT1, 33 LQT2, and 2 LQT3) families with mutation results.
Conclusions—Typical ST-T–wave patterns are present in the majority of genotyped LQTS patients and can be used to identify LQT1, LQT2, and possibly LQT3 genotypes. Family-grouped ECG analysis improves genotype identification accuracy. This approach can simplify genetic screening by targeting the gene for initial study. The multiple ST-T patterns in each genotype raise questions regarding the pathophysiology and regulation of repolarization in LQTS.
Key Words: genetics • long-QT syndrome • electrocardiography • waves
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|
|
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|
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|
|
|
|
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|
|
|
|
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|
|
|
|
|
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|
|
|
|
|
|
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|
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|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
 |
|
 K. Gima and Y. Rudy Ionic Current Basis of Electrocardiographic Waveforms: A Model Study Circ. Res., May 3, 2002; 90(8): 889 - 896. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. di Bernardo, A. Murray, A. A.M. Wilde, and D. M. Roden T-Wave Shape in Clinical Research Response Circulation, October 9, 2001; 104 (15): e80 - e80. [Full Text] [PDF]
|
|
|
|
|
|
A. A.M. Wilde and D. Escande LQT genotype-phenotype relationships: patients and patches Cardiovasc Res, September 1, 2001; 51(4): 627 - 629. [Full Text] [PDF]
|
|
|
|
 |
|
 ECG Patterns Identify Genotypes in Patients with Long-QT Syndrome Journal Watch Cardiology, February 2, 2001; 2001(202): 1 - 1. [Full Text]
|
|
|
|
|
|
A. A. M. Wilde and D. M. Roden Predicting the Long-QT Genotype From Clinical Data : From Sense to Science Circulation, December 5, 2000; 102(23): 2796 - 2798. [Full Text] [PDF]
|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|