Abstract 3393: The Common LQT1 Mutation KCNQ1/A341V Predicts High Risk of Cardiac Events in Different Ethnic Backgrounds
We recently suggested that the KCNQ1-A341V mutation, identified in a large LQT1 founder population in South Africa (SA), is associated with a risk of becoming symptomatic much higher than that reported for large series of LQT1 patients (pts). A341V is a mutational hot spot identified worldwide. We are assessing if the observed clinical phenotype was specific to the SA kindred or is specific to the mutation and is therefore shared by other A341V families. In the present ongoing study we have collected data on 40 A341V pts from 13 families in several countries (Japan, Germany, USA, Netherlands and Italy). The mean age of the pts (50% females) is 30± 20 years. Only 11 (27.5 %) are asymptomatic but 5 of them are still below age 10. Syncope, cardiac arrest or sudden cardiac death (SCD, n=4, all before age 20 and off-therapy) occurred in 29/40 (72.5%) with a mean age at first event of 9±6 years, similar to that of the SA population (7±4). The cumulative probability of suffering a first cardiac event before β-blocker therapy and before age 40 (see figure⇓) was very similar to that of the SA kindred (63 % vs 65 %; 71% vs 81%, respectively by age 10 and 20; log-rank, p=0.22) and very different from that of 355 LQT1 patients with a diversity of KCNQ1 mutations (Priori et al. NEJM 2003). These worldwide data confirm our initial South African observation and demonstrate that KCNQ1-A341V is indeed a mutation of unusual severity within the LQT1 group which includes many patients asymptomatic through life. The A341V carriers require full-dose beta blockers, to which they appear to respond very well.