TY - JOUR
T1 - Genotype-specific QT correction for heart rate and the risk of life-threatening cardiac events in adolescents with congenital long-QT syndrome
AU - Barsheshet, Alon
AU - Peterson, Derick R.
AU - Moss, Arthur J.
AU - Schwartz, Peter J.
AU - Kaufman, Elizabeth S.
AU - McNitt, Scott
AU - Polonsky, Slava
AU - Buber, Jonathan
AU - Zareba, Wojciech
AU - Robinson, Jennifer L.
AU - Ackerman, Michael J.
AU - Benhorin, Jesaia
AU - Towbin, Jeffrey A.
AU - Vincent, G. Michael
AU - Zhang, Li
AU - Goldenberg, Ilan
PY - 2011/8
Y1 - 2011/8
N2 - Background: A prolonged QT interval corrected for heart rate (QTc) is a major risk factor in patients with long QT syndrome (LQTS). However, heart raterelated risk in this genetic disorder differs among genotypes. Objective: This study hypothesized that risk assessment in LQTS patients should incorporate genotype-specific QT correction for heart rate. Methods: The independent contribution of 4 repolarization measures (the absolute QT interval, and Bazett's, Fridericia's, and Framingham's correction formulas) to the risk of aborted cardiac arrest or sudden cardiac death during adolescence, before and after further adjustment for the RR interval, was assessed in 727 LQTS type 1 and 582 LQTS type 2 patients. Improved QT/RR correction was calculated using a Cox model, dividing the coefficient on log(RR) by that on log(QT). Results: Multivariate analysis demonstrated that in LQTS type 1 patients 100-ms increments in the absolute QT interval were associated with a 3.3-fold increase in the risk of life-threatening cardiac events (P =.020), and 100-ms decrements in the RR interval were associated with a further 1.9-fold increase in the risk (P =.007), whereas in LQTS type 2 patients, resting heart rate was not a significant risk factor (hazard ratio 1.11; P =.51; P value for heart rate × genotype interaction =.036). Accordingly, analysis of an improved QT correction formula showed that patients with the LQTS type 1 genotype required a greater degree of QT correction for heart rate (improved QTc = QT/RR 0.8) than LQTS type 2 patients (improved QTc = QT/RR 0.2). Conclusion: Our findings suggest that risk stratification for life-threatening cardiac events in LQTS patients can be improved by incorporating genotype-specific QT correction for heart rate.
AB - Background: A prolonged QT interval corrected for heart rate (QTc) is a major risk factor in patients with long QT syndrome (LQTS). However, heart raterelated risk in this genetic disorder differs among genotypes. Objective: This study hypothesized that risk assessment in LQTS patients should incorporate genotype-specific QT correction for heart rate. Methods: The independent contribution of 4 repolarization measures (the absolute QT interval, and Bazett's, Fridericia's, and Framingham's correction formulas) to the risk of aborted cardiac arrest or sudden cardiac death during adolescence, before and after further adjustment for the RR interval, was assessed in 727 LQTS type 1 and 582 LQTS type 2 patients. Improved QT/RR correction was calculated using a Cox model, dividing the coefficient on log(RR) by that on log(QT). Results: Multivariate analysis demonstrated that in LQTS type 1 patients 100-ms increments in the absolute QT interval were associated with a 3.3-fold increase in the risk of life-threatening cardiac events (P =.020), and 100-ms decrements in the RR interval were associated with a further 1.9-fold increase in the risk (P =.007), whereas in LQTS type 2 patients, resting heart rate was not a significant risk factor (hazard ratio 1.11; P =.51; P value for heart rate × genotype interaction =.036). Accordingly, analysis of an improved QT correction formula showed that patients with the LQTS type 1 genotype required a greater degree of QT correction for heart rate (improved QTc = QT/RR 0.8) than LQTS type 2 patients (improved QTc = QT/RR 0.2). Conclusion: Our findings suggest that risk stratification for life-threatening cardiac events in LQTS patients can be improved by incorporating genotype-specific QT correction for heart rate.
KW - Aborted cardiac arrest
KW - Heart rate
KW - Long QT syndrome
KW - QT correction
KW - Risk factor
KW - Sudden cardiac death
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U2 - 10.1016/j.hrthm.2011.03.009
DO - 10.1016/j.hrthm.2011.03.009
M3 - Article
C2 - 21397043
AN - SCOPUS:79960833880
SN - 1547-5271
VL - 8
SP - 1207
EP - 1213
JO - Heart rhythm
JF - Heart rhythm
IS - 8
ER -