Risk of life-threatening cardiac events among patients with long QT syndrome and multiple mutations

Jamie Mullally, Ilan Goldenberg, Arthur J. Moss, Coeli M. Lopes, Michael John Ackerman, Wojciech Zareba, Scott McNitt, Jennifer L. Robinson, Jesaia Benhorin, Elizabeth S. Kaufman, Jeffrey A. Towbin, Alon Barsheshet

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Background: Patients with long QT syndrome (LQTS) who harbor multiple mutations (i.e. ≥ 2 mutations in ≥ 1 LQTS-susceptibility gene) may experience increased risk for life-threatening cardiac events. Objectives: The present study was designed to compare the clinical course of LQTS patients with multiple mutations to those with a single mutation. Methods: The risk for life-threatening cardiac events (comprising aborted cardiac arrest, implantable defibrillator shock, or sudden cardiac death) from birth through age 40 years, by the presence of multiple vs. single mutations, was assessed among 403 patients from the LQTS Registry. Results: Patients with multiple mutations (n=57) exhibited a longer QTc at enrollment compared with those with a single mutation (mean±SD: 506±72 vs. 480±56 msec, respectively; P=0.003) and had a higher rate of life threatening cardiac events during follow-up (23% vs. 11%, respectively; p=0.031). Consistently, multivariate analysis demonstrated that patients with multiple mutations had a 2.3-fold (P=0.015) increased risk for life threatening cardiac events as compared to patients with a single mutation. The presence of multiple mutations in a single LQTS gene was associated with a 3.2-fold increased risk for life threatening cardiac events (P=0.010) whereas the risk associated with multiple mutation status involving>1 LQTS gene was not significantly different from the risk associated with a single mutation (HR 1.7, P=0.26). Conclusions: LQTS patients with multiple mutations have a greater risk for life-threatening cardiac events as compared to patients with a single mutation.

Original languageEnglish (US)
Pages (from-to)378-382
Number of pages5
JournalHeart Rhythm
Volume10
Issue number3
DOIs
StatePublished - Mar 2013

Fingerprint

Long QT Syndrome
Mutation
Romano-Ward Syndrome
Genes
Implantable Defibrillators
Sudden Cardiac Death
Heart Arrest

Keywords

  • Aborted cardiac arrest
  • Long QT syndrome
  • Mutation
  • Risk factor
  • Sudden cardiac death

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Mullally, J., Goldenberg, I., Moss, A. J., Lopes, C. M., Ackerman, M. J., Zareba, W., ... Barsheshet, A. (2013). Risk of life-threatening cardiac events among patients with long QT syndrome and multiple mutations. Heart Rhythm, 10(3), 378-382. https://doi.org/10.1016/j.hrthm.2012.11.006

Risk of life-threatening cardiac events among patients with long QT syndrome and multiple mutations. / Mullally, Jamie; Goldenberg, Ilan; Moss, Arthur J.; Lopes, Coeli M.; Ackerman, Michael John; Zareba, Wojciech; McNitt, Scott; Robinson, Jennifer L.; Benhorin, Jesaia; Kaufman, Elizabeth S.; Towbin, Jeffrey A.; Barsheshet, Alon.

In: Heart Rhythm, Vol. 10, No. 3, 03.2013, p. 378-382.

Research output: Contribution to journalArticle

Mullally, J, Goldenberg, I, Moss, AJ, Lopes, CM, Ackerman, MJ, Zareba, W, McNitt, S, Robinson, JL, Benhorin, J, Kaufman, ES, Towbin, JA & Barsheshet, A 2013, 'Risk of life-threatening cardiac events among patients with long QT syndrome and multiple mutations', Heart Rhythm, vol. 10, no. 3, pp. 378-382. https://doi.org/10.1016/j.hrthm.2012.11.006
Mullally, Jamie ; Goldenberg, Ilan ; Moss, Arthur J. ; Lopes, Coeli M. ; Ackerman, Michael John ; Zareba, Wojciech ; McNitt, Scott ; Robinson, Jennifer L. ; Benhorin, Jesaia ; Kaufman, Elizabeth S. ; Towbin, Jeffrey A. ; Barsheshet, Alon. / Risk of life-threatening cardiac events among patients with long QT syndrome and multiple mutations. In: Heart Rhythm. 2013 ; Vol. 10, No. 3. pp. 378-382.
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abstract = "Background: Patients with long QT syndrome (LQTS) who harbor multiple mutations (i.e. ≥ 2 mutations in ≥ 1 LQTS-susceptibility gene) may experience increased risk for life-threatening cardiac events. Objectives: The present study was designed to compare the clinical course of LQTS patients with multiple mutations to those with a single mutation. Methods: The risk for life-threatening cardiac events (comprising aborted cardiac arrest, implantable defibrillator shock, or sudden cardiac death) from birth through age 40 years, by the presence of multiple vs. single mutations, was assessed among 403 patients from the LQTS Registry. Results: Patients with multiple mutations (n=57) exhibited a longer QTc at enrollment compared with those with a single mutation (mean±SD: 506±72 vs. 480±56 msec, respectively; P=0.003) and had a higher rate of life threatening cardiac events during follow-up (23{\%} vs. 11{\%}, respectively; p=0.031). Consistently, multivariate analysis demonstrated that patients with multiple mutations had a 2.3-fold (P=0.015) increased risk for life threatening cardiac events as compared to patients with a single mutation. The presence of multiple mutations in a single LQTS gene was associated with a 3.2-fold increased risk for life threatening cardiac events (P=0.010) whereas the risk associated with multiple mutation status involving>1 LQTS gene was not significantly different from the risk associated with a single mutation (HR 1.7, P=0.26). Conclusions: LQTS patients with multiple mutations have a greater risk for life-threatening cardiac events as compared to patients with a single mutation.",
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AU - Zareba, Wojciech

AU - McNitt, Scott

AU - Robinson, Jennifer L.

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AB - Background: Patients with long QT syndrome (LQTS) who harbor multiple mutations (i.e. ≥ 2 mutations in ≥ 1 LQTS-susceptibility gene) may experience increased risk for life-threatening cardiac events. Objectives: The present study was designed to compare the clinical course of LQTS patients with multiple mutations to those with a single mutation. Methods: The risk for life-threatening cardiac events (comprising aborted cardiac arrest, implantable defibrillator shock, or sudden cardiac death) from birth through age 40 years, by the presence of multiple vs. single mutations, was assessed among 403 patients from the LQTS Registry. Results: Patients with multiple mutations (n=57) exhibited a longer QTc at enrollment compared with those with a single mutation (mean±SD: 506±72 vs. 480±56 msec, respectively; P=0.003) and had a higher rate of life threatening cardiac events during follow-up (23% vs. 11%, respectively; p=0.031). Consistently, multivariate analysis demonstrated that patients with multiple mutations had a 2.3-fold (P=0.015) increased risk for life threatening cardiac events as compared to patients with a single mutation. The presence of multiple mutations in a single LQTS gene was associated with a 3.2-fold increased risk for life threatening cardiac events (P=0.010) whereas the risk associated with multiple mutation status involving>1 LQTS gene was not significantly different from the risk associated with a single mutation (HR 1.7, P=0.26). Conclusions: LQTS patients with multiple mutations have a greater risk for life-threatening cardiac events as compared to patients with a single mutation.

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KW - Mutation

KW - Risk factor

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