Effectiveness and Limitations of b-Blocker Therapy in Congenital Long-QT Syndrome

Background—b-blockers are routinely prescribed in congenital long-QT syndrome (LQTS), but the effectiveness and limitations of b-blockers in this disorder have not been evaluated. Methods and Results—The study population comprised 869 LQTS patients treated with b-blockers. Effectiveness of b-blockers was analyzed during matched periods before and after starting b-blocker therapy, and by survivorship methods to determine factors associated with cardiac events while on prescribed b-blockers. After initiation of b-blockers, there was a significant (P,0.001) reduction in the rate of cardiac events in probands (0.9761.42 to 0.3160.86 events per year) and in affected family members (0.2660.84 to 0.1560.69 events per year) during 5-year matched periods. On-therapy survivorship analyses revealed that patients with cardiac symptoms before b-blockers (n5598) had a hazard ratio of 5.8 (95 % CI, 3.7 to 9.1) for recurrent cardiac events (syncope, aborted cardiac arrest, or death) during b-blocker therapy compared with asymptomatic patients; 32 % of these symptomatic patients will have another cardiac event within 5 years while on prescribed b-blockers. Patients with a history of aborted cardiac arrest before starting b-blockers (n5113) had a hazard ratio of 12.9 (95 % CI, 4.7 to 35.5) for aborted cardiac arrest or death while on prescribed b-blockers compared with asymptomatic patients; 14 % of these patients will have another arrest (aborted or fatal) within 5 years on b-blockers. Conclusions—b-blockers are associated with a significant reduction in cardiac events in LQTS patients. However, syncope, aborted cardiac arrest, and LQTS-related death continue to occur while patients are on prescribed b-blockers, particularly i