Age- and sex-related differences in clinical manifestations in patients with congenital long-QT syndrome: Findings from the international LQTS registry

Emanuela H. Locati, Wojciech Zareba, Arthur J. Moss, Peter J. Schwartz, G. Michael Vincent, Michael H. Lehmann, Jeffrey Towbin, Silvia G. Priori, Carlo Napolitano, Jennifer L. Robinson, Mark Andrews, Katherine Timothy, W. Jackson Hall

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Abstract

Background: Unexplained female predominance is observed in long-QT syndrome (LQTS), a congenital autosomal disorder with prolonged repolarization and syncope or sudden death due to ventricular tachyarrhythmias. Our objectives were to evaluate age- and sex-related differences in events among LQTS patients referred to the LQTS International Registry. Methods and Results: Age- and sex-related occurrence of events was analyzed in 479 probands (70% females) and 1041 affected family members (QT(c) >440 ms, 58% females). LQTS-gene mutations were identified in 162 patients: 69 LQT1 carriers (KVLQT1 on 11p15.5), 62 LQT2 carriers (HERG on 7q35-36), and 31 LQT3 carriers (SCN5A on 3p21-24). Females predominated among 366 probands (71% females) and 230 symptomatic family members (62% females). Male probands were younger than females at first event (8±7 versus 14±10 years, P<0.0001) and had higher event rates by age 15 years than females (74% versus 51%, P<0.0001). Affected family members had similar findings. By Cox analysis adjusting for QT(c) duration, the hazard ratio for female probands of experiencing events by age 15 years was 0.48 (P<0.001), and it was 1.87 (P=0.09) by age 15 to 40 years. In female family members, the hazard ratio was 0.58 (P<0.001) by age 15 years, and it was 3.25 (P<0.001) by age 15 to 40 years. The event rate was higher in male than female LQT1 carriers (69% versus 32%, P=0.001). No age-sex difference in event rate was detected in LQT2 and LQT3 carriers. Conclusions: Among LQTS patients, the risk of cardiac events was higher in males until puberty and higher in females during adulthood. The same pattern was evident among LQT1 gene carriers. Unknown sex factors modulate QT duration and arrhythmic events, with preliminary evidence of gene-specific differences in age-sex modulation.

Original languageEnglish (US)
Pages (from-to)2237-2244
Number of pages8
JournalCirculation
Volume97
Issue number22
DOIs
StatePublished - Jun 9 1998

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Long QT Syndrome
Sex Characteristics
Registries
Genes
Sex Factors
Congenital, Hereditary, and Neonatal Diseases and Abnormalities
Syncope
Puberty
Sudden Death
Tachycardia

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Locati, E. H., Zareba, W., Moss, A. J., Schwartz, P. J., Michael Vincent, G., Lehmann, M. H., ... Hall, W. J. (1998). Age- and sex-related differences in clinical manifestations in patients with congenital long-QT syndrome: Findings from the international LQTS registry. Circulation, 97(22), 2237-2244. https://doi.org/10.1161/01.CIR.97.22.2237

Age- and sex-related differences in clinical manifestations in patients with congenital long-QT syndrome : Findings from the international LQTS registry. / Locati, Emanuela H.; Zareba, Wojciech; Moss, Arthur J.; Schwartz, Peter J.; Michael Vincent, G.; Lehmann, Michael H.; Towbin, Jeffrey; Priori, Silvia G.; Napolitano, Carlo; Robinson, Jennifer L.; Andrews, Mark; Timothy, Katherine; Hall, W. Jackson.

In: Circulation, Vol. 97, No. 22, 09.06.1998, p. 2237-2244.

Research output: Contribution to journalArticle

Locati, EH, Zareba, W, Moss, AJ, Schwartz, PJ, Michael Vincent, G, Lehmann, MH, Towbin, J, Priori, SG, Napolitano, C, Robinson, JL, Andrews, M, Timothy, K & Hall, WJ 1998, 'Age- and sex-related differences in clinical manifestations in patients with congenital long-QT syndrome: Findings from the international LQTS registry', Circulation, vol. 97, no. 22, pp. 2237-2244. https://doi.org/10.1161/01.CIR.97.22.2237
Locati, Emanuela H. ; Zareba, Wojciech ; Moss, Arthur J. ; Schwartz, Peter J. ; Michael Vincent, G. ; Lehmann, Michael H. ; Towbin, Jeffrey ; Priori, Silvia G. ; Napolitano, Carlo ; Robinson, Jennifer L. ; Andrews, Mark ; Timothy, Katherine ; Hall, W. Jackson. / Age- and sex-related differences in clinical manifestations in patients with congenital long-QT syndrome : Findings from the international LQTS registry. In: Circulation. 1998 ; Vol. 97, No. 22. pp. 2237-2244.
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abstract = "Background: Unexplained female predominance is observed in long-QT syndrome (LQTS), a congenital autosomal disorder with prolonged repolarization and syncope or sudden death due to ventricular tachyarrhythmias. Our objectives were to evaluate age- and sex-related differences in events among LQTS patients referred to the LQTS International Registry. Methods and Results: Age- and sex-related occurrence of events was analyzed in 479 probands (70{\%} females) and 1041 affected family members (QT(c) >440 ms, 58{\%} females). LQTS-gene mutations were identified in 162 patients: 69 LQT1 carriers (KVLQT1 on 11p15.5), 62 LQT2 carriers (HERG on 7q35-36), and 31 LQT3 carriers (SCN5A on 3p21-24). Females predominated among 366 probands (71{\%} females) and 230 symptomatic family members (62{\%} females). Male probands were younger than females at first event (8±7 versus 14±10 years, P<0.0001) and had higher event rates by age 15 years than females (74{\%} versus 51{\%}, P<0.0001). Affected family members had similar findings. By Cox analysis adjusting for QT(c) duration, the hazard ratio for female probands of experiencing events by age 15 years was 0.48 (P<0.001), and it was 1.87 (P=0.09) by age 15 to 40 years. In female family members, the hazard ratio was 0.58 (P<0.001) by age 15 years, and it was 3.25 (P<0.001) by age 15 to 40 years. The event rate was higher in male than female LQT1 carriers (69{\%} versus 32{\%}, P=0.001). No age-sex difference in event rate was detected in LQT2 and LQT3 carriers. Conclusions: Among LQTS patients, the risk of cardiac events was higher in males until puberty and higher in females during adulthood. The same pattern was evident among LQT1 gene carriers. Unknown sex factors modulate QT duration and arrhythmic events, with preliminary evidence of gene-specific differences in age-sex modulation.",
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T2 - Findings from the international LQTS registry

AU - Locati, Emanuela H.

AU - Zareba, Wojciech

AU - Moss, Arthur J.

AU - Schwartz, Peter J.

AU - Michael Vincent, G.

AU - Lehmann, Michael H.

AU - Towbin, Jeffrey

AU - Priori, Silvia G.

AU - Napolitano, Carlo

AU - Robinson, Jennifer L.

AU - Andrews, Mark

AU - Timothy, Katherine

AU - Hall, W. Jackson

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N2 - Background: Unexplained female predominance is observed in long-QT syndrome (LQTS), a congenital autosomal disorder with prolonged repolarization and syncope or sudden death due to ventricular tachyarrhythmias. Our objectives were to evaluate age- and sex-related differences in events among LQTS patients referred to the LQTS International Registry. Methods and Results: Age- and sex-related occurrence of events was analyzed in 479 probands (70% females) and 1041 affected family members (QT(c) >440 ms, 58% females). LQTS-gene mutations were identified in 162 patients: 69 LQT1 carriers (KVLQT1 on 11p15.5), 62 LQT2 carriers (HERG on 7q35-36), and 31 LQT3 carriers (SCN5A on 3p21-24). Females predominated among 366 probands (71% females) and 230 symptomatic family members (62% females). Male probands were younger than females at first event (8±7 versus 14±10 years, P<0.0001) and had higher event rates by age 15 years than females (74% versus 51%, P<0.0001). Affected family members had similar findings. By Cox analysis adjusting for QT(c) duration, the hazard ratio for female probands of experiencing events by age 15 years was 0.48 (P<0.001), and it was 1.87 (P=0.09) by age 15 to 40 years. In female family members, the hazard ratio was 0.58 (P<0.001) by age 15 years, and it was 3.25 (P<0.001) by age 15 to 40 years. The event rate was higher in male than female LQT1 carriers (69% versus 32%, P=0.001). No age-sex difference in event rate was detected in LQT2 and LQT3 carriers. Conclusions: Among LQTS patients, the risk of cardiac events was higher in males until puberty and higher in females during adulthood. The same pattern was evident among LQT1 gene carriers. Unknown sex factors modulate QT duration and arrhythmic events, with preliminary evidence of gene-specific differences in age-sex modulation.

AB - Background: Unexplained female predominance is observed in long-QT syndrome (LQTS), a congenital autosomal disorder with prolonged repolarization and syncope or sudden death due to ventricular tachyarrhythmias. Our objectives were to evaluate age- and sex-related differences in events among LQTS patients referred to the LQTS International Registry. Methods and Results: Age- and sex-related occurrence of events was analyzed in 479 probands (70% females) and 1041 affected family members (QT(c) >440 ms, 58% females). LQTS-gene mutations were identified in 162 patients: 69 LQT1 carriers (KVLQT1 on 11p15.5), 62 LQT2 carriers (HERG on 7q35-36), and 31 LQT3 carriers (SCN5A on 3p21-24). Females predominated among 366 probands (71% females) and 230 symptomatic family members (62% females). Male probands were younger than females at first event (8±7 versus 14±10 years, P<0.0001) and had higher event rates by age 15 years than females (74% versus 51%, P<0.0001). Affected family members had similar findings. By Cox analysis adjusting for QT(c) duration, the hazard ratio for female probands of experiencing events by age 15 years was 0.48 (P<0.001), and it was 1.87 (P=0.09) by age 15 to 40 years. In female family members, the hazard ratio was 0.58 (P<0.001) by age 15 years, and it was 3.25 (P<0.001) by age 15 to 40 years. The event rate was higher in male than female LQT1 carriers (69% versus 32%, P=0.001). No age-sex difference in event rate was detected in LQT2 and LQT3 carriers. Conclusions: Among LQTS patients, the risk of cardiac events was higher in males until puberty and higher in females during adulthood. The same pattern was evident among LQT1 gene carriers. Unknown sex factors modulate QT duration and arrhythmic events, with preliminary evidence of gene-specific differences in age-sex modulation.

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