TY - JOUR
T1 - Trigger-specific risk factors and response to therapy in long QT syndrome type 2
AU - Kim, James A.
AU - Lopes, Coeli M.
AU - Moss, Arthur J.
AU - McNitt, Scott
AU - Barsheshet, Alon
AU - Robinson, Jennifer L.
AU - Zareba, Wojciech
AU - Ackerman, Michael J.
AU - Kaufman, Elizabeth S.
AU - Towbin, Jeffrey A.
AU - Vincent, Michael
AU - Goldenberg, Ilan
N1 - Funding Information:
J.A. Kim, C.M. Lopes, and I. Goldenberg contributed equally to the original concept and authorship of this investigation. This work was supported by Research Grants HL-33843 and HL-51618 from the National Institutes of Health , Bethesda, Maryland.
PY - 2010/12
Y1 - 2010/12
N2 - Background Cardiac events in patients with long QT syndrome type 2 (LQT2) are predominately associated with sudden arousal. However, exercise-induced events also occur in this population. Objective The purpose of this study was to test the hypothesis that risk factors show a trigger-specific association with cardiac events in LQT2 patients. Methods The study population consisted of 634 genetically confirmed LQT2 patients from the U.S. portion of the International LQTS Registry. Multivariate Cox proportional hazards regression analysis was used to determine the independent contribution of clinical and genetic risk factors to the first occurrence of trigger-specific cardiac events, categorized as arousal, exercise-induced, and nonarousal/nonexercise, from birth through age 40 years. Results Study patients experienced 204 cardiac events during follow-up, of which 44% were associated with arousal triggers, 13% with exercise activity, and 43% with nonexercise/nonarousal triggers. Risk factors for arousal-triggered cardiac events included gender (female:male >13 years: hazard ratio [HR] 9.10, P <.001) and the presence of pore-loop mutations (HR 2.19, P = .009). In contrast, nonpore-loop transmembrane mutations were the predominant risk factor for exercise-triggered events (HR 6.84, P <.001), whereas gender was not a significant risk factor for this endpoint. Nonexercise/nonarousal events were associated with heterogeneous causes. Risk factors for this endpoint included gender, mutation location and type, and prolonged QTc (<500 m) Beta-blocker therapy was associated with a pronounced reduction in the risk for exercise-triggered events (HR 0.29, P <.01) but had a nonsignificant effect on the risk for arousal and nonexercise/nonarousal events. Conclusion The study findings suggest that management of patients with the LQT2 genotype should use a trigger-specific approach to risk assessment and medical therapy.
AB - Background Cardiac events in patients with long QT syndrome type 2 (LQT2) are predominately associated with sudden arousal. However, exercise-induced events also occur in this population. Objective The purpose of this study was to test the hypothesis that risk factors show a trigger-specific association with cardiac events in LQT2 patients. Methods The study population consisted of 634 genetically confirmed LQT2 patients from the U.S. portion of the International LQTS Registry. Multivariate Cox proportional hazards regression analysis was used to determine the independent contribution of clinical and genetic risk factors to the first occurrence of trigger-specific cardiac events, categorized as arousal, exercise-induced, and nonarousal/nonexercise, from birth through age 40 years. Results Study patients experienced 204 cardiac events during follow-up, of which 44% were associated with arousal triggers, 13% with exercise activity, and 43% with nonexercise/nonarousal triggers. Risk factors for arousal-triggered cardiac events included gender (female:male >13 years: hazard ratio [HR] 9.10, P <.001) and the presence of pore-loop mutations (HR 2.19, P = .009). In contrast, nonpore-loop transmembrane mutations were the predominant risk factor for exercise-triggered events (HR 6.84, P <.001), whereas gender was not a significant risk factor for this endpoint. Nonexercise/nonarousal events were associated with heterogeneous causes. Risk factors for this endpoint included gender, mutation location and type, and prolonged QTc (<500 m) Beta-blocker therapy was associated with a pronounced reduction in the risk for exercise-triggered events (HR 0.29, P <.01) but had a nonsignificant effect on the risk for arousal and nonexercise/nonarousal events. Conclusion The study findings suggest that management of patients with the LQT2 genotype should use a trigger-specific approach to risk assessment and medical therapy.
KW - Beta-blocker
KW - Ion channel mutation
KW - Long QT syndrome
KW - Risk factor
KW - Sudden cardiac death
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U2 - 10.1016/j.hrthm.2010.09.011
DO - 10.1016/j.hrthm.2010.09.011
M3 - Article
C2 - 20850565
AN - SCOPUS:78650095336
SN - 1547-5271
VL - 7
SP - 1797
EP - 1805
JO - Heart rhythm
JF - Heart rhythm
IS - 12
ER -