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 A.
AU - Barsheshet, Alon
N1 - Funding Information:
This work was supported in part by research grants HL-33843 and HL-51618 to the University of Rochester Medical Center from the National Institutes of Health, Bethesda, MD. Dr. Moss received a research grant from GeneDx. Dr. Kaufman received research grant from CardioDx and St Jude Medical. Dr. Ackerman has a consulting relationship and license agreement/royalty arrangement with Transgenomic and received consultant fees from Medtronic, Biotronik, Boston Scientific, and St Jude Medical.
PY - 2013/3
Y1 - 2013/3
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.
KW - Aborted cardiac arrest
KW - Long QT syndrome
KW - Mutation
KW - Risk factor
KW - Sudden cardiac death
UR - http://www.scopus.com/inward/record.url?scp=84875295625&partnerID=8YFLogxK
U2 - 10.1016/j.hrthm.2012.11.006
DO - 10.1016/j.hrthm.2012.11.006
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C2 - 23174487
AN - SCOPUS:84875295625
SN - 1547-5271
VL - 10
SP - 378
EP - 382
JO - Heart Rhythm
JF - Heart Rhythm
IS - 3
ER -