The long QT syndrome. Prospective longitudinal study of 328 families.

BACKGROUND: The Long QT Syndrome (LQTS) is an infrequently occurring familial disorder in which affected individuals have electrocardiographic QT interval prolongation and a propensity to ventricular tachyarrhythmic syncope and sudden death. We prospectively investigated the clinical characteristics and the long-term course of 3,343 individuals from 328 families in which one or more members were identified as affected with LQTS (QTc greater than 0.44 sec1/2). METHODS AND RESULTS: The first member of a family to be identified with LQTS, the proband, was usually brought to medical attention because of a syncopal episode during childhood or teenage years. Probands (n = 328) were younger at first contact (age 21 +/- 15 years), more likely to be female (69%), and had a higher frequency of preenrollment syncope or cardiac arrest with resuscitation (80%), congenital deafness (7%), a resting heart rate less than 60 beats/min (31%), QTc greater than or equal to 0.50 sec1/2 (52%), and a history of ventricular tachyarrhythmia (47%) than other affected (n = 688) and unaffected (n = 1,004) family members. Arrhythmogenic syncope often occurred in association with acute physical, emotional, or auditory arousal. The syncopal episodes were frequently misinterpreted as a seizure disorder. By age 12 years, 50% of the probands had experienced at least one syncopal episode or death. The rates of postenrollment syncope (one or more episodes) and probable LQTS-related death (before age 50 years) for probands (n = 235; average follow-up 54 months per patient) were 5.0% per year and 0.9% per year, respectively; these event rates were considerably higher than those observed among affected and unaffected family members. CONCLUSIONS: Among 232 probands and 1,264 family members with prospective follow-up, three factors made significant independent contributions to the risk of subsequent syncope or probable LQTS-related death before age 50 years, whichever occurred first (Cox hazard ratio; 95% confidence limits): 1) QTc (1.052; 1.017, 1.088), 2) history of cardiac event (3.1; 1.3, 7.2), and 3) heart rate (1.017; 1.004, 1.031). The findings from this prospective longitudinal study highlight the clinical features, risk factors, and course of LQTS.