Identification of Electrocardiographic Characteristics in Silent Carriers of Mutant KCNQ1 gene

Background:
Congenital long-QT syndrome (LQTS) is an inherited channelopathy characterized by a prolonged corrected QT interval and is associated with an increased predisposition for polymorphic ventricular arrhythmias and sudden cardiac death (SCD) in young subjects. About 10-40% of family members are silent mutation carriers but still exhibit a significant increase in the risk of SCD compared with unaffected family members. Clinical identification of silent carriers is challenging.

Objective:
The aim of this study is to identify electrocardiographic characteristics using exercise test and holter monitoring of silent carriers of mutant KCNQ1 gene.

Methods:
We compared QT length and shortening and T wave morphology during ECG, exercise test and 12 leads holter in 14 silent carriers of KCNQ1 mutation with 14 healthy subjects.

Results:
When compared to healthy control group, heterozygous silent carriers of mutant KCNQ1 gene presented inadequate ability of QT interval adaptation in response to rapid changes in heart rates (increase of 10 beats per minute in less than 60 seconds). Median QT shortening of 12.3 msec in the carriers vs 15.5 msec in the control, p=0.013. The value of the area under T wave divided by T wave amplitude at a constant heart rate was significantly higher in the carrier group compared to our control group (86.7 vs 75.9, p=0.04). In multivariate analysis QT shortening of less than 14.3 msec while the heart rate increases by 10 beats in less than 60 minutes was a risk factor for silent carrier (HR 9.9, CI 1.1-71.1, p=0.035).

Conclusion:
Abnormal QT shortening in respond to rapid changes in heart rate, and increase in area under T wave divided by T wave amplitude, may be useful tools for detecting LQTS1 concealed carriers