Abstract 18100: Risk of Cardiac Events in Genotype-Negative Family Members of Patients with Long QT Syndrome
Background: Current practice for the diagnosis of congenital long-QT syndrome (LQTS) includes genetic testing of family members of identified LQTS probands. However, the clinical course of individuals who are found negative for the LQTS-causing family mutation is unknown.
Methods: The present study comprised 2878 subjects from the International LQTS Registry who were genetically tested and found negative for the family proband's LQTS-causing mutation. Multivariate Cox proportional hazards regression modeling was used to assess the risk for cardiac events (including syncope, aborted cardiac arrest [ACA], or sudden cardiac death [SCD]) and life-threatening events (ACA or SCD) from birth through age 40 years in this population.
Results: The median QTc of study subjects was 420 msec (range: 350 msec to 520 msec; interquartile-range: 400 msec to 440 msec). During follow-up, the overall cumulative probability of cardiac events was 13%. The rate of cardiac events was significantly higher among women than among men (Figure). Consistently, multivariate analysis showed that women had a significant 67% (p=0.008) increase in the risk of cardiac events as compared with men, whereas a prolonged QTc (>=470 msec) was not associated with a statistically significant increase in the risk of cardiac events (HR=1.23; p=0.14). Only 2 study subjects (0.07%) experienced ACA or SCD during 40 years of follow-up.
Conclusions: Genotype-negative family members of LQTS patients experience a relatively high rate of cardiac events, that is more pronounced among women. However, the cardiac event rate is dominated by nonfatal syncopal episodes, whereas the risk of life-threatening events in this population is near-zero. These findings suggest a nonarrhythmogenic etiology of syncope in individuals who are found negative for the LQTS-causing family mutation.
- © 2010 by American Heart Association, Inc.