Modulating effects of age and gender on the clinical course of long QT syndrome by genotype

Wojciech Zareba, Arthur J. Moss, Emanuela H. Locati, Michael H. Lehmann, Derick R. Peterson, W. Jackson Hall, Peter J. Schwartz, G. Michael Vincent, Silvia G. Priori, Jesaia Benhorin, Jeffrey Towbin, Jennifer L. Robinson, Mark L. Andrews, Carlo Napolitano, Katherine Timothy, Li Zhang, Aharon Medina

Research output: Contribution to journalArticle

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Abstract

OBJECTIVES: We aimed to determine whether long QT syndrome (LQTS) genotype has a differential effect on clinical course of disease in male and female children and adults after adjustment for QTc duration. BACKGROUND: Genotype influences clinical course of the LQTS; however, data on the effect of age and gender on this association are limited. METHODS: The LQTS genotype, QTc duration, and follow-up were determined in 243 cases of LQTS caused by the KCNQ1 potassium channel gene mutations (LQT1), 209 cases of LQTS caused by the HERG potassium channel gene mutations (LQT2), and 81 cases of LQTS caused by the SCN5A sodium channel gene mutation (LQT3) gene carriers. The probability of cardiac events (syncope, aborted cardiac arrest, or sudden death) was analyzed by genotype, gender, and age (children ≤ 15 years and adults 16 to 40 years). In addition, the risk of sudden death and lethality of cardiac events were evaluated in 1,075 LQT1, 976 LQT2, and 324 LQT3 family members from families with known genotype. RESULTS: During childhood, the risk of cardiac events was significantly higher in LQT1 males than in LQT1 females (hazard ratio [HR] = 1.72), whereas there was no significant gender-related difference in the risk of cardiac events among LQT2 and LQT3 carriers. During adulthood, LQT2 females (HR = 3.71) and LQT1 females (HR = 3.35) had a significantly higher risk of cardiac events than respective males. The lethality of cardiac events was highest in LQT3 males and females (19% and 18%), and higher in LQT1 and LQT2 males (5% and 6%) than in LQT1 and LQT2 females (2% for both). CONCLUSIONS: Age and gender have different, genotype-specific modulating effects on the probability of cardiac events and electrocardiographic presentation in LQT1 and LQT2 patients.

Original languageEnglish (US)
Pages (from-to)103-109
Number of pages7
JournalJournal of the American College of Cardiology
Volume42
Issue number1
DOIs
StatePublished - Jul 2 2003
Externally publishedYes

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Long QT Syndrome
Genotype
Mutation
Genes
KCNQ1 Potassium Channel
Sodium Channels
Potassium Channels
Sudden Cardiac Death
Syncope
Sudden Death
Heart Arrest

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

Cite this

Zareba, W., Moss, A. J., Locati, E. H., Lehmann, M. H., Peterson, D. R., Hall, W. J., ... Medina, A. (2003). Modulating effects of age and gender on the clinical course of long QT syndrome by genotype. Journal of the American College of Cardiology, 42(1), 103-109. https://doi.org/10.1016/S0735-1097(03)00554-0

Modulating effects of age and gender on the clinical course of long QT syndrome by genotype. / Zareba, Wojciech; Moss, Arthur J.; Locati, Emanuela H.; Lehmann, Michael H.; Peterson, Derick R.; Hall, W. Jackson; Schwartz, Peter J.; Vincent, G. Michael; Priori, Silvia G.; Benhorin, Jesaia; Towbin, Jeffrey; Robinson, Jennifer L.; Andrews, Mark L.; Napolitano, Carlo; Timothy, Katherine; Zhang, Li; Medina, Aharon.

In: Journal of the American College of Cardiology, Vol. 42, No. 1, 02.07.2003, p. 103-109.

Research output: Contribution to journalArticle

Zareba, W, Moss, AJ, Locati, EH, Lehmann, MH, Peterson, DR, Hall, WJ, Schwartz, PJ, Vincent, GM, Priori, SG, Benhorin, J, Towbin, J, Robinson, JL, Andrews, ML, Napolitano, C, Timothy, K, Zhang, L & Medina, A 2003, 'Modulating effects of age and gender on the clinical course of long QT syndrome by genotype', Journal of the American College of Cardiology, vol. 42, no. 1, pp. 103-109. https://doi.org/10.1016/S0735-1097(03)00554-0
Zareba, Wojciech ; Moss, Arthur J. ; Locati, Emanuela H. ; Lehmann, Michael H. ; Peterson, Derick R. ; Hall, W. Jackson ; Schwartz, Peter J. ; Vincent, G. Michael ; Priori, Silvia G. ; Benhorin, Jesaia ; Towbin, Jeffrey ; Robinson, Jennifer L. ; Andrews, Mark L. ; Napolitano, Carlo ; Timothy, Katherine ; Zhang, Li ; Medina, Aharon. / Modulating effects of age and gender on the clinical course of long QT syndrome by genotype. In: Journal of the American College of Cardiology. 2003 ; Vol. 42, No. 1. pp. 103-109.
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abstract = "OBJECTIVES: We aimed to determine whether long QT syndrome (LQTS) genotype has a differential effect on clinical course of disease in male and female children and adults after adjustment for QTc duration. BACKGROUND: Genotype influences clinical course of the LQTS; however, data on the effect of age and gender on this association are limited. METHODS: The LQTS genotype, QTc duration, and follow-up were determined in 243 cases of LQTS caused by the KCNQ1 potassium channel gene mutations (LQT1), 209 cases of LQTS caused by the HERG potassium channel gene mutations (LQT2), and 81 cases of LQTS caused by the SCN5A sodium channel gene mutation (LQT3) gene carriers. The probability of cardiac events (syncope, aborted cardiac arrest, or sudden death) was analyzed by genotype, gender, and age (children ≤ 15 years and adults 16 to 40 years). In addition, the risk of sudden death and lethality of cardiac events were evaluated in 1,075 LQT1, 976 LQT2, and 324 LQT3 family members from families with known genotype. RESULTS: During childhood, the risk of cardiac events was significantly higher in LQT1 males than in LQT1 females (hazard ratio [HR] = 1.72), whereas there was no significant gender-related difference in the risk of cardiac events among LQT2 and LQT3 carriers. During adulthood, LQT2 females (HR = 3.71) and LQT1 females (HR = 3.35) had a significantly higher risk of cardiac events than respective males. The lethality of cardiac events was highest in LQT3 males and females (19{\%} and 18{\%}), and higher in LQT1 and LQT2 males (5{\%} and 6{\%}) than in LQT1 and LQT2 females (2{\%} for both). CONCLUSIONS: Age and gender have different, genotype-specific modulating effects on the probability of cardiac events and electrocardiographic presentation in LQT1 and LQT2 patients.",
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T1 - Modulating effects of age and gender on the clinical course of long QT syndrome by genotype

AU - Zareba, Wojciech

AU - Moss, Arthur J.

AU - Locati, Emanuela H.

AU - Lehmann, Michael H.

AU - Peterson, Derick R.

AU - Hall, W. Jackson

AU - Schwartz, Peter J.

AU - Vincent, G. Michael

AU - Priori, Silvia G.

AU - Benhorin, Jesaia

AU - Towbin, Jeffrey

AU - Robinson, Jennifer L.

AU - Andrews, Mark L.

AU - Napolitano, Carlo

AU - Timothy, Katherine

AU - Zhang, Li

AU - Medina, Aharon

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N2 - OBJECTIVES: We aimed to determine whether long QT syndrome (LQTS) genotype has a differential effect on clinical course of disease in male and female children and adults after adjustment for QTc duration. BACKGROUND: Genotype influences clinical course of the LQTS; however, data on the effect of age and gender on this association are limited. METHODS: The LQTS genotype, QTc duration, and follow-up were determined in 243 cases of LQTS caused by the KCNQ1 potassium channel gene mutations (LQT1), 209 cases of LQTS caused by the HERG potassium channel gene mutations (LQT2), and 81 cases of LQTS caused by the SCN5A sodium channel gene mutation (LQT3) gene carriers. The probability of cardiac events (syncope, aborted cardiac arrest, or sudden death) was analyzed by genotype, gender, and age (children ≤ 15 years and adults 16 to 40 years). In addition, the risk of sudden death and lethality of cardiac events were evaluated in 1,075 LQT1, 976 LQT2, and 324 LQT3 family members from families with known genotype. RESULTS: During childhood, the risk of cardiac events was significantly higher in LQT1 males than in LQT1 females (hazard ratio [HR] = 1.72), whereas there was no significant gender-related difference in the risk of cardiac events among LQT2 and LQT3 carriers. During adulthood, LQT2 females (HR = 3.71) and LQT1 females (HR = 3.35) had a significantly higher risk of cardiac events than respective males. The lethality of cardiac events was highest in LQT3 males and females (19% and 18%), and higher in LQT1 and LQT2 males (5% and 6%) than in LQT1 and LQT2 females (2% for both). CONCLUSIONS: Age and gender have different, genotype-specific modulating effects on the probability of cardiac events and electrocardiographic presentation in LQT1 and LQT2 patients.

AB - OBJECTIVES: We aimed to determine whether long QT syndrome (LQTS) genotype has a differential effect on clinical course of disease in male and female children and adults after adjustment for QTc duration. BACKGROUND: Genotype influences clinical course of the LQTS; however, data on the effect of age and gender on this association are limited. METHODS: The LQTS genotype, QTc duration, and follow-up were determined in 243 cases of LQTS caused by the KCNQ1 potassium channel gene mutations (LQT1), 209 cases of LQTS caused by the HERG potassium channel gene mutations (LQT2), and 81 cases of LQTS caused by the SCN5A sodium channel gene mutation (LQT3) gene carriers. The probability of cardiac events (syncope, aborted cardiac arrest, or sudden death) was analyzed by genotype, gender, and age (children ≤ 15 years and adults 16 to 40 years). In addition, the risk of sudden death and lethality of cardiac events were evaluated in 1,075 LQT1, 976 LQT2, and 324 LQT3 family members from families with known genotype. RESULTS: During childhood, the risk of cardiac events was significantly higher in LQT1 males than in LQT1 females (hazard ratio [HR] = 1.72), whereas there was no significant gender-related difference in the risk of cardiac events among LQT2 and LQT3 carriers. During adulthood, LQT2 females (HR = 3.71) and LQT1 females (HR = 3.35) had a significantly higher risk of cardiac events than respective males. The lethality of cardiac events was highest in LQT3 males and females (19% and 18%), and higher in LQT1 and LQT2 males (5% and 6%) than in LQT1 and LQT2 females (2% for both). CONCLUSIONS: Age and gender have different, genotype-specific modulating effects on the probability of cardiac events and electrocardiographic presentation in LQT1 and LQT2 patients.

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