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Risk for Life-Threatening Cardiac Events in Patients With Genotype-Confirmed Long-QT Syndrome and Normal-Range Corrected QT Intervals

Goldenberg, Ilan; Horr, Samuel; Moss, Arthur J.; Lopes, Coeli M.; Barsheshet, Alon; McNitt, Scott; Zareba, Wojciech; Andrews, Mark L.; Robinson, Jennifer L. and Locati, Emanuela H., et al. (2010) In Journal of the American College of Cardiology 57(1). p.51-59
Abstract
Objectives This study was designed to assess the clinical course and to identify risk factors for life-threatening events in patients with long-QT syndrome (LQTS) with normal corrected QT (QTc) intervals. Background Current data regarding the outcome of patients with concealed LQTS are limited. Methods Clinical and genetic risk factors for aborted cardiac arrest (ACA) or sudden cardiac death (SCD) from birth through age 40 years were examined in 3,386 genotyped subjects from 7 multinational LQTS registries, categorized as LQTS with normal-range QTc (<= 440 ms [n = 469]), LQTS with prolonged QTc interval (>440 ms [ n = 1,392]), and unaffected family members (genotyped negative with <= 440 ms [ n = 1,525]). Results The cumulative... (More)
Objectives This study was designed to assess the clinical course and to identify risk factors for life-threatening events in patients with long-QT syndrome (LQTS) with normal corrected QT (QTc) intervals. Background Current data regarding the outcome of patients with concealed LQTS are limited. Methods Clinical and genetic risk factors for aborted cardiac arrest (ACA) or sudden cardiac death (SCD) from birth through age 40 years were examined in 3,386 genotyped subjects from 7 multinational LQTS registries, categorized as LQTS with normal-range QTc (<= 440 ms [n = 469]), LQTS with prolonged QTc interval (>440 ms [ n = 1,392]), and unaffected family members (genotyped negative with <= 440 ms [ n = 1,525]). Results The cumulative probability of ACA or SCD in patients with LQTS with normal-range QTc intervals (4%) was significantly lower than in those with prolonged QTc intervals (15%) (p < 0.001) but higher than in unaffected family members (0.4%) (p < 0.001). Risk factors ACA or SCD in patients with normal-range QTc intervals included mutation characteristics (transmembrane-missense vs. nontransmembrane or nonmissense mutations: hazard ratio: 6.32; p = 0.006) and the LQTS genotypes (LQTS type 1: LQTS type 2, hazard ratio: 9.88; p = 0.03; LQTS type 3: LQTS type 2, hazard ratio: 8.04; p = 0.07), whereas clinical factors, including sex and QTc duration, were associated with a significant increase in the risk for ACA or SCD only in patients with prolonged QTc intervals (female age >13 years, hazard ratio: 1.90; p = 0.002; QTc duration, 8% risk increase per 10-ms increment; p = 0.002). Conclusions Genotype-confirmed patients with concealed LQTS make up about 25% of the at-risk LQTS population. Genetic data, including information regarding mutation characteristics and the LQTS genotype, identify increased risk for ACA or SCD in this overall lower risk LQTS subgroup. (J Am Coll Cardiol 2011;57:51-9) (C) 2011 by the American College of Cardiology Foundation (Less)
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published
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keywords
sudden cardiac death, long-QT syndrome, corrected QT interval
in
Journal of the American College of Cardiology
volume
57
issue
1
pages
51 - 59
publisher
Elsevier USA
external identifiers
  • wos:000285577900008
  • scopus:78650549525
ISSN
0735-1097
DOI
10.1016/j.jacc.2010.07.038
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English
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c187f568-4a37-4c18-862c-b632ed9ca53a (old id 1815206)
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2011-03-02 12:48:09
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2018-05-29 10:16:37
@article{c187f568-4a37-4c18-862c-b632ed9ca53a,
  abstract     = {Objectives This study was designed to assess the clinical course and to identify risk factors for life-threatening events in patients with long-QT syndrome (LQTS) with normal corrected QT (QTc) intervals. Background Current data regarding the outcome of patients with concealed LQTS are limited. Methods Clinical and genetic risk factors for aborted cardiac arrest (ACA) or sudden cardiac death (SCD) from birth through age 40 years were examined in 3,386 genotyped subjects from 7 multinational LQTS registries, categorized as LQTS with normal-range QTc (&lt;= 440 ms [n = 469]), LQTS with prolonged QTc interval (&gt;440 ms [ n = 1,392]), and unaffected family members (genotyped negative with &lt;= 440 ms [ n = 1,525]). Results The cumulative probability of ACA or SCD in patients with LQTS with normal-range QTc intervals (4%) was significantly lower than in those with prolonged QTc intervals (15%) (p &lt; 0.001) but higher than in unaffected family members (0.4%) (p &lt; 0.001). Risk factors ACA or SCD in patients with normal-range QTc intervals included mutation characteristics (transmembrane-missense vs. nontransmembrane or nonmissense mutations: hazard ratio: 6.32; p = 0.006) and the LQTS genotypes (LQTS type 1: LQTS type 2, hazard ratio: 9.88; p = 0.03; LQTS type 3: LQTS type 2, hazard ratio: 8.04; p = 0.07), whereas clinical factors, including sex and QTc duration, were associated with a significant increase in the risk for ACA or SCD only in patients with prolonged QTc intervals (female age &gt;13 years, hazard ratio: 1.90; p = 0.002; QTc duration, 8% risk increase per 10-ms increment; p = 0.002). Conclusions Genotype-confirmed patients with concealed LQTS make up about 25% of the at-risk LQTS population. Genetic data, including information regarding mutation characteristics and the LQTS genotype, identify increased risk for ACA or SCD in this overall lower risk LQTS subgroup. (J Am Coll Cardiol 2011;57:51-9) (C) 2011 by the American College of Cardiology Foundation},
  author       = {Goldenberg, Ilan and Horr, Samuel and Moss, Arthur J. and Lopes, Coeli M. and Barsheshet, Alon and McNitt, Scott and Zareba, Wojciech and Andrews, Mark L. and Robinson, Jennifer L. and Locati, Emanuela H. and Ackerman, Michael J. and Benhorin, Jesaia and Kaufman, Elizabeth S. and Napolitano, Carlo and Platonov, Pyotr and Priori, Silvia G. and Qi, Ming and Schwartz, Peter J. and Shimizu, Wataru and Towbin, Jeffrey A. and Vincent, G. Michael and Wilde, Arthur A. M. and Zhang, Li},
  issn         = {0735-1097},
  keyword      = {sudden cardiac death,long-QT syndrome,corrected QT interval},
  language     = {eng},
  number       = {1},
  pages        = {51--59},
  publisher    = {Elsevier USA},
  series       = {Journal of the American College of Cardiology},
  title        = {Risk for Life-Threatening Cardiac Events in Patients With Genotype-Confirmed Long-QT Syndrome and Normal-Range Corrected QT Intervals},
  url          = {http://dx.doi.org/10.1016/j.jacc.2010.07.038},
  volume       = {57},
  year         = {2010},
}