Open AccessClinical aspects of the three major genetic forms of long QT syndrome ( LQT 1, LQT 2, LQT 3)
Author(s) -
Kutyifa Valentina,
Daimee Usama A.,
McNitt Scott,
Polonsky Bronislava,
Lowenstein Charles,
Cutter Kris,
Lopes Coeli,
Zareba Wojciech,
Moss Arthur J.
Publication year - 2018
Publication title -
annals of noninvasive electrocardiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.494
H-Index - 48
eISSN - 1542-474X
pISSN - 1082-720X
DOI - 10.1111/anec.12537
Subject(s) - medicine , long qt syndrome , cardiology , proportional hazards model , proband , anesthesia , qt interval , mutation , biochemistry , chemistry , gene
Background A comprehensive report on the clinical course of the three major genotypes of the long QT syndrome ( LQTS ) in a large U.S. patient cohort is lacking. Methods Our study consisted of 1,923 U.S. subjects from the Rochester‐based LQTS Registry with genotype‐positive LQT 1 ( n = 879), LQT 2 ( n = 807), and LQT 3 ( n = 237). We evaluated the risk of a first cardiac event (syncope, aborted cardiac arrest, or sudden cardiac death, whichever occurred first) from birth through age 50 years. Cox proportional hazards regression models incorporating clinical covariates were used to assess genotype‐specific risk of cardiac events. Results For all three genotypes, the cumulative probability of a first cardiac event increased most markedly during adolescence. Multivariate analysis identified proband status and QT c > 500 ms as predictors of cardiac events in all three genotypes, and males <14 years and females >14 years as predictors of cardiac events in LQT 1 and LQT 2 only. Beta‐blockers significantly reduced the risk of cardiac events in LQT 1 ( HR : 0.49, p = .002) and LQT 2 patients ( HR : 0.48, p = .001). A trend toward beta‐blocker benefit in reducing cardiac events was found in LQT 3 females ( HR : 0.32, p = .078), but not in LQT 3 males ( HR : 1.37, p = .611). Conclusion Risk factors and outcomes in LQTS patients varied by genotype. In all three genotypes, proband status and prolonged QT c were risk factors for cardiac events. Younger males and older females experienced increased risk in LQT 1 and LQT 2 only. Beta‐blockers were most effective in reducing cardiac events in LQT 1 and LQT 2, with a potential benefit in LQT 3 females.