Abstract 16413: Mutation Specific QTc Variance in Congenital Long QT Syndrome: A Clinical Predictor of Cardiac Events
Background: Multiple ion channel mutations account for the congenital Long QT Syndrome (LQTS). However, among carriers of the same mutation, the individual QTc may vary widely. Currently neither the mechanism nor the implications of this variable penetrance are well understood. We hypothesized that assessment of QTc variance among LQTS carriers of the same mutation provides incremental prognostic information to the patient-specific QTc.
Methods: The study population comprised 1206 LQTS patients with 95 different mutations, with ≥5 individuals per mutation. Multivariate Cox proportional hazards regression modeling was used to assess the effect of mutation-specific standard deviation of QTc (QTcSD) on the risk of cardiac events (comprising syncope, aborted cardiac arrest, and sudden cardiac death) from birth through age 40 years.
Results: Assessment of mutation-specific QTc showed large differences within the same mutations (Figure 1 histograms). Multivariate analysis showed that mutation specific QTcSD was associated with a significant increase in the risk for cardiac events (Hazard Ratio = 1.17; 17% increase in risk per 20 msec increment in QTcSD [p = 0.01]) after adjustment for the patient's individual QTc duration. Consistently, Kaplan-Meier survival analysis showed that carriers of mutations with >median QTcSD (≥45 msec) experienced a significant increase in the risk of cardiac events compared with carriers of mutations with a narrower QTcSD (p<0.001; Figure 1).
Conclusions: Our findings suggest that mutations with a wider variation in QTc duration are associated with a significant increase in the risk of cardiac events, independently of individual QTc assessment.
- © 2011 by American Heart Association, Inc.