Abstract 2765: Natural History and Genetic Features of Short QT Syndrome
Short QT syndrome (SQTS) is a rare genetic disorder characterized by abnormally short QT interval and high risk of sudden cardiac death (SCD). This study addresses the issue of natural history, genetics and electrocardiographic features in the largest prospective SQTS cohort (47 individuals in 24 families). Diagnosis was made in the presence of QTc interval ≤ 350 ms w./out history of cardiac arrest (CA) or SCD without structural abnormalities. Median age at diagnosis was 27 years (range 4–56); mean QTc was 323±17 ms, 22/36 (61%) pts had abnormal T wave (n=17) and/or J point elevation (n=8) and/or QRS slurring (n=3); at a mean observation time of 30±14 years, 22 (47%) pts had cardiac events: 11 SCD, 4 resuscitated CA and 7 syncopal episodes. Median age at SCD or CA was 19 (range 0 – 48) years (4 death/CA occurred in the first year of life). The Kaplan Meyer curve shows survival-free interval before drugs. Triggers for the 15 death/CA were exercise (44%) and rest (56%). Eight pts were treated with quinidine (250 mg bid) that prolonged QTc: from 320±18 ms to 380±18 ms (p<0.005). Genetic screening on KCNH2, KCNQ1 and KCNJ2 genes was positive in 3/24 probands and 3 family members. Interestingly, genotyped pts (n=6) presented significantly shorter QTc than non-genotyped pts (303±13 ms vs. 328±14 ms, p<0.001). In summary our data show that SQTS is a severe disorder with high risk of cardiac arrest occurring from infancy to adulthood. The yield of genetic testing is low (13%) suggesting genetic heterogeneity, but patients harboring a genetic mutation have more severe phenotype. The use of quinidine can help to normalize the QTc although its effect on cardiac events remains to be assessed.