Comparison of Electrocardiographic QTc Duration in Patients With Supravalvar Aortic Stenosis With Versus Without Williams Syndrome

Cardiovascular abnormalities in Williams syndrome (WS) are largely attributable to elastin haploinsufficiency resulting from a large deletion of the elastin-containing region on chromosome 7q11.23. The risk of sudden death in patients with WS is 25- to 100-fold greater than that in the general population. The corrected QT (QTc) interval is prolonged in 14% of patients with WS. Patients with nonsyndromic supravalvar aortic stenosis (NSVAS) have elastin mutations resulting in elastin haploinsufficiency and a vascular phenotype nearly identical to that of WS. No previous studies have evaluated the QTc duration in NSVAS. A retrospective review of all electrocardiograms (ECGs) performed on consecutive patients with NSVAS at Arkansas Childrenʹs Hospital from January 1, 1985 to January 1, 2012 was completed. ECGs with nonsinus rhythm or unmeasurable intervals were excluded. The ECGs were read by 1 reader who was unaware of previous readings. A QTc interval of ≥460 ms was defined as prolonged. The NSVAS cohort was compared to previously published WS and control groups using the mixed model for continuous electrocardiographic variables and the generalized estimating equation for binary indicators for prolonged QTc. The generalized estimating equation used bootstrapping with 1,000 replicates. A total of 300 ECGs (median 6, range 1 to 27) from the 35 identified patients with NSVAS met the inclusion criteria. A total of 482 ECGs from patients with WS and 1,522 ECGs from controls were included. The mean age of the patients with NSVAS at ECG was 7.3 ± 6.9 years; 64% were male. The mean QTc duration was 409 ± 20 ms in the NSVAS group, 418 ± 17 ms in the control group (p <0.001), and 436 ± 27 ms in the WS group (p <0.001 compared to the control group). The prevalence of QTc prolongation was 0.3% in the NSVAS group, 2.0% in the control group (p <0.001), and 14.8% in the WS group (p <0.001 compared to controls). No patients with NSVAS died. In conclusion, cardiac repolarization is normal in patients with NSVAS. Elastin haploinsufficiency does not appear to be the etiology of QTc prolongation in patients with WS. The possible contribution of other genes on 7q11.23 to QTc prolongation in WS should be investigated.