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Architectural T-Wave Analysis and Identification of On-Therapy Breakthrough Arrhythmic Risk in Type 1 and Type 2 Long-QT Syndrome
A. Sugrue, RK. Rohatgi, PA. Noseworthy, V. Kremen, JM. Bos, B. Qiang, Y. Sapir, ZI. Attia, CG. Scott, P. Brady, SJ. Asirvatham, PA. Friedman, MJ. Ackerman,
Circulation. Arrhythmia and electrophysiology.
2017 ;
10 (11) :
.
Language English Country United States
Document type Journal Article
Persistent link
https://www.medvik.cz/link/bmc18016226
Online
Full text
NLK
Free Medical Journals
from 2008 to 1 year ago
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from 2008-04-01
- MeSH
- Action Potentials MeSH
- Anti-Arrhythmia Agents therapeutic use MeSH
- Time Factors MeSH
- Child MeSH
- Adult MeSH
- Electrocardiography * MeSH
- Phenotype MeSH
- Genetic Predisposition to Disease MeSH
- Risk Assessment MeSH
- Kaplan-Meier Estimate MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Predictive Value of Tests MeSH
- Heart Conduction System drug effects physiopathology MeSH
- Proportional Hazards Models MeSH
- Risk Factors MeSH
- Romano-Ward Syndrome diagnosis drug therapy genetics physiopathology MeSH
- Chi-Square Distribution MeSH
- Heart Rate drug effects MeSH
- Long QT Syndrome diagnosis drug therapy genetics physiopathology MeSH
- Treatment Outcome MeSH
- Check Tag
- Child MeSH
- Adult MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
BACKGROUND: Although the hallmark of long-QT syndrome (LQTS) is abnormal cardiac repolarization, there are varying degrees of phenotypic expression and arrhythmic risk. Our aim was to evaluate the performance of a morphological T-wave analysis program in defining breakthrough LQTS arrhythmic risk beyond the QTc value. METHODS AND RESULTS: We analyzed 407 genetically confirmed patients with LQT1 (n=246; 43% men) and LQT2 (n=161; 41% men) over the mean follow-up period of 6.4±3.9 years. ECG analysis was conducted using a novel, proprietary T-wave analysis program. Time to a LQTS-associated cardiac event was analyzed using Cox proportional hazards regression methods. Twenty-three patients experienced ≥1 defined breakthrough cardiac arrhythmic events with 5- and 10-year event rates of 4% and 7%. Two independent predictors of future LQTS-associated cardiac events from the surface ECG were identified: left slope of T wave in lead V6 (hazard ratio=0.40 [0.24-0.69]; P<0.001) and T-wave center of gravity x axis (last 25% of wave) in lead I (hazard ratio=1.90 [1.21-2.99]; P=0.005), C statistic of 0.77 (0.65-0.89). When added to the QTc (C statistic 0.68 for QTc alone), discrimination improved to 0.78. Genotype analysis showed weaker association between these T-wave variables and LQT1-triggered events while these features were stronger in patients with LQT2 and significantly outperformed the QTc (C statistic, 0.82 [0.71-0.93]). CONCLUSION: Detailed morphological analysis of the T wave provides novel insights into risk of breakthrough arrhythmic events in LQTS, particularly LQT2. This observation has the potential to guide clinical decision making and further refine risk stratification.
Czech Institute of Informatics Robotics and Cybernetics Czech Technical University Prague
Electrical and Computer Engineering Ben Gurion University of the Negev Beer Sheva Israel
References provided by Crossref.org
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- $a Sugrue, Alan $u From the Division of Heart Rhythm Services, Department of Cardiovascular Diseases (A.S., P.A.N., V.K., B.Q., Z.I.A., P.B., S.J.A., P.A.F., M.J.A.), Division of Pediatric Cardiology, Department of Pediatric and Adolescent Medicine (R.K.R., J.M.B., S.J.A., M.J.A.), and Department of Molecular Pharmacology and Experimental Therapeutics (J.M.B., M.J.A.), Windland Smith Rice Sudden Death Genomics Laboratory, and Division of Biomedical Statistics and Informatics (C.G.S.), Mayo Clinic, Rochester, MN; Czech Institute of Informatics, Robotics, and Cybernetics, Czech Technical University in Prague (V.K.); and Electrical and Computer Engineering, Ben-Gurion University of the Negev, Beer Sheva, Israel (Y.S.).
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- $a BACKGROUND: Although the hallmark of long-QT syndrome (LQTS) is abnormal cardiac repolarization, there are varying degrees of phenotypic expression and arrhythmic risk. Our aim was to evaluate the performance of a morphological T-wave analysis program in defining breakthrough LQTS arrhythmic risk beyond the QTc value. METHODS AND RESULTS: We analyzed 407 genetically confirmed patients with LQT1 (n=246; 43% men) and LQT2 (n=161; 41% men) over the mean follow-up period of 6.4±3.9 years. ECG analysis was conducted using a novel, proprietary T-wave analysis program. Time to a LQTS-associated cardiac event was analyzed using Cox proportional hazards regression methods. Twenty-three patients experienced ≥1 defined breakthrough cardiac arrhythmic events with 5- and 10-year event rates of 4% and 7%. Two independent predictors of future LQTS-associated cardiac events from the surface ECG were identified: left slope of T wave in lead V6 (hazard ratio=0.40 [0.24-0.69]; P<0.001) and T-wave center of gravity x axis (last 25% of wave) in lead I (hazard ratio=1.90 [1.21-2.99]; P=0.005), C statistic of 0.77 (0.65-0.89). When added to the QTc (C statistic 0.68 for QTc alone), discrimination improved to 0.78. Genotype analysis showed weaker association between these T-wave variables and LQT1-triggered events while these features were stronger in patients with LQT2 and significantly outperformed the QTc (C statistic, 0.82 [0.71-0.93]). CONCLUSION: Detailed morphological analysis of the T wave provides novel insights into risk of breakthrough arrhythmic events in LQTS, particularly LQT2. This observation has the potential to guide clinical decision making and further refine risk stratification.
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- $a Rohatgi, Ram K $u From the Division of Heart Rhythm Services, Department of Cardiovascular Diseases (A.S., P.A.N., V.K., B.Q., Z.I.A., P.B., S.J.A., P.A.F., M.J.A.), Division of Pediatric Cardiology, Department of Pediatric and Adolescent Medicine (R.K.R., J.M.B., S.J.A., M.J.A.), and Department of Molecular Pharmacology and Experimental Therapeutics (J.M.B., M.J.A.), Windland Smith Rice Sudden Death Genomics Laboratory, and Division of Biomedical Statistics and Informatics (C.G.S.), Mayo Clinic, Rochester, MN; Czech Institute of Informatics, Robotics, and Cybernetics, Czech Technical University in Prague (V.K.); and Electrical and Computer Engineering, Ben-Gurion University of the Negev, Beer Sheva, Israel (Y.S.).
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