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 J. Ackerman, Wojciech Zareba, Scott McNitt, Jennifer L. Robinson, Jesaia Benhorin, Elizabeth S. Kaufman, Jeffrey 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 1 2013
Externally publishedYes

Fingerprint

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

All Science Journal Classification (ASJC) codes

  • 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 J.; Zareba, Wojciech; McNitt, Scott; Robinson, Jennifer L.; Benhorin, Jesaia; Kaufman, Elizabeth S.; Towbin, Jeffrey; Barsheshet, Alon.

In: Heart Rhythm, Vol. 10, No. 3, 01.03.2013, 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, J & 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 J, Goldenberg I, Moss AJ, Lopes CM, Ackerman MJ, Zareba W et al. Risk of life-threatening cardiac events among patients with long QT syndrome and multiple mutations. Heart Rhythm. 2013 Mar 1;10(3):378-382. https://doi.org/10.1016/j.hrthm.2012.11.006
Mullally, Jamie ; Goldenberg, Ilan ; Moss, Arthur J. ; Lopes, Coeli M. ; Ackerman, Michael J. ; Zareba, Wojciech ; McNitt, Scott ; Robinson, Jennifer L. ; Benhorin, Jesaia ; Kaufman, Elizabeth S. ; Towbin, Jeffrey ; 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.
@article{8665d15040fb48479112553e83b14216,
title = "Risk of life-threatening cardiac events among patients with long QT syndrome and multiple mutations",
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.",
author = "Jamie Mullally and Ilan Goldenberg and Moss, {Arthur J.} and Lopes, {Coeli M.} and Ackerman, {Michael J.} and Wojciech Zareba and Scott McNitt and Robinson, {Jennifer L.} and Jesaia Benhorin and Kaufman, {Elizabeth S.} and Jeffrey Towbin and Alon Barsheshet",
year = "2013",
month = "3",
day = "1",
doi = "10.1016/j.hrthm.2012.11.006",
language = "English (US)",
volume = "10",
pages = "378--382",
journal = "Heart Rhythm",
issn = "1547-5271",
publisher = "Elsevier",
number = "3",

}

TY - JOUR

T1 - Risk of life-threatening cardiac events among patients with long QT syndrome and multiple mutations

AU - Mullally, Jamie

AU - Goldenberg, Ilan

AU - Moss, Arthur J.

AU - Lopes, Coeli M.

AU - Ackerman, Michael J.

AU - Zareba, Wojciech

AU - McNitt, Scott

AU - Robinson, Jennifer L.

AU - Benhorin, Jesaia

AU - Kaufman, Elizabeth S.

AU - Towbin, Jeffrey

AU - Barsheshet, Alon

PY - 2013/3/1

Y1 - 2013/3/1

N2 - 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.

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.

UR - http://www.scopus.com/inward/record.url?scp=84875295625&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84875295625&partnerID=8YFLogxK

U2 - 10.1016/j.hrthm.2012.11.006

DO - 10.1016/j.hrthm.2012.11.006

M3 - Article

C2 - 23174487

AN - SCOPUS:84875295625

VL - 10

SP - 378

EP - 382

JO - Heart Rhythm

JF - Heart Rhythm

SN - 1547-5271

IS - 3

ER -