Risk for life-threatening cardiac events in patients with genotype-confirmed long-QT syndrome and normal-range corrected QT intervals

Ilan Goldenberg, Samuel Horr, Arthur J. Moss, Coeli M. Lopes, Alon Barsheshet, Scott McNitt, Wojciech Zareba, Mark L. Andrews, Jennifer L. Robinson, Emanuela H. Locati, Michael J. Ackerman, Jesaia Benhorin, Elizabeth S. Kaufman, Carlo Napolitano, Pyotr G. Platonov, Silvia G. Priori, Ming Qi, Peter J. Schwartz, Wataru Shimizu, Jeffrey TowbinG. Michael Vincent, Arthur A.M. Wilde, Li Zhang

Research output: Contribution to journalArticle

155 Citations (Scopus)

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 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.

Original languageEnglish (US)
Pages (from-to)51-59
Number of pages9
JournalJournal of the American College of Cardiology
Volume57
Issue number1
DOIs
StatePublished - Jan 4 2011

Fingerprint

Long QT Syndrome
Reference Values
Genotype
Sudden Cardiac Death
Heart Arrest
Andersen Syndrome
Registries
Parturition
Mutation

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

Cite this

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.; Locati, Emanuela H.; Ackerman, Michael J.; Benhorin, Jesaia; Kaufman, Elizabeth S.; Napolitano, Carlo; Platonov, Pyotr G.; Priori, Silvia G.; Qi, Ming; Schwartz, Peter J.; Shimizu, Wataru; Towbin, Jeffrey; Vincent, G. Michael; Wilde, Arthur A.M.; Zhang, Li.

In: Journal of the American College of Cardiology, Vol. 57, No. 1, 04.01.2011, p. 51-59.

Research output: Contribution to journalArticle

Goldenberg, I, Horr, S, Moss, AJ, Lopes, CM, Barsheshet, A, McNitt, S, Zareba, W, Andrews, ML, Robinson, JL, Locati, EH, Ackerman, MJ, Benhorin, J, Kaufman, ES, Napolitano, C, Platonov, PG, Priori, SG, Qi, M, Schwartz, PJ, Shimizu, W, Towbin, J, Vincent, GM, Wilde, AAM & Zhang, L 2011, 'Risk for life-threatening cardiac events in patients with genotype-confirmed long-QT syndrome and normal-range corrected QT intervals', Journal of the American College of Cardiology, vol. 57, no. 1, pp. 51-59. https://doi.org/10.1016/j.jacc.2010.07.038
Goldenberg, Ilan ; Horr, Samuel ; Moss, Arthur J. ; Lopes, Coeli M. ; Barsheshet, Alon ; McNitt, Scott ; Zareba, Wojciech ; Andrews, Mark L. ; Robinson, Jennifer L. ; Locati, Emanuela H. ; Ackerman, Michael J. ; Benhorin, Jesaia ; Kaufman, Elizabeth S. ; Napolitano, Carlo ; Platonov, Pyotr G. ; Priori, Silvia G. ; Qi, Ming ; Schwartz, Peter J. ; Shimizu, Wataru ; Towbin, Jeffrey ; Vincent, G. Michael ; Wilde, Arthur A.M. ; Zhang, Li. / Risk for life-threatening cardiac events in patients with genotype-confirmed long-QT syndrome and normal-range corrected QT intervals. In: Journal of the American College of Cardiology. 2011 ; Vol. 57, No. 1. pp. 51-59.
@article{f48e3eec439741539b060c4a7fe04216,
title = "Risk for life-threatening cardiac events in patients with genotype-confirmed long-QT syndrome and normal-range corrected QT intervals",
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 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.",
author = "Ilan Goldenberg and Samuel Horr and Moss, {Arthur J.} and Lopes, {Coeli M.} and Alon Barsheshet and Scott McNitt and Wojciech Zareba and Andrews, {Mark L.} and Robinson, {Jennifer L.} and Locati, {Emanuela H.} and Ackerman, {Michael J.} and Jesaia Benhorin and Kaufman, {Elizabeth S.} and Carlo Napolitano and Platonov, {Pyotr G.} and Priori, {Silvia G.} and Ming Qi and Schwartz, {Peter J.} and Wataru Shimizu and Jeffrey Towbin and Vincent, {G. Michael} and Wilde, {Arthur A.M.} and Li Zhang",
year = "2011",
month = "1",
day = "4",
doi = "10.1016/j.jacc.2010.07.038",
language = "English (US)",
volume = "57",
pages = "51--59",
journal = "Journal of the American College of Cardiology",
issn = "0735-1097",
publisher = "Elsevier USA",
number = "1",

}

TY - JOUR

T1 - Risk for life-threatening cardiac events in patients with genotype-confirmed long-QT syndrome and normal-range corrected QT intervals

AU - Goldenberg, Ilan

AU - Horr, Samuel

AU - Moss, Arthur J.

AU - Lopes, Coeli M.

AU - Barsheshet, Alon

AU - McNitt, Scott

AU - Zareba, Wojciech

AU - Andrews, Mark L.

AU - Robinson, Jennifer L.

AU - Locati, Emanuela H.

AU - Ackerman, Michael J.

AU - Benhorin, Jesaia

AU - Kaufman, Elizabeth S.

AU - Napolitano, Carlo

AU - Platonov, Pyotr G.

AU - Priori, Silvia G.

AU - Qi, Ming

AU - Schwartz, Peter J.

AU - Shimizu, Wataru

AU - Towbin, Jeffrey

AU - Vincent, G. Michael

AU - Wilde, Arthur A.M.

AU - Zhang, Li

PY - 2011/1/4

Y1 - 2011/1/4

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=78650549525&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=78650549525&partnerID=8YFLogxK

U2 - 10.1016/j.jacc.2010.07.038

DO - 10.1016/j.jacc.2010.07.038

M3 - Article

C2 - 21185501

AN - SCOPUS:78650549525

VL - 57

SP - 51

EP - 59

JO - Journal of the American College of Cardiology

JF - Journal of the American College of Cardiology

SN - 0735-1097

IS - 1

ER -