Background—β-blockers are routinely prescribed in congenital long-QT syndrome (LQTS), but the effectiveness and limitations of β-blockers in this disorder have not been evaluated.

Methods and Results—The study population comprised 869 LQTS patients treated with β-blockers. Effectiveness of β-blockers was analyzed during matched periods before and after starting β-blocker therapy, and by survivorship methods to determine factors associated with cardiac events while on prescribed β-blockers. After initiation of β-blockers, there was a significant (P<0.001) reduction in the rate of cardiac events in probands (0.97±1.42 to 0.31±0.86 events per year) and in affected family members (0.26±0.84 to 0.15±0.69 events per year) during 5-year matched periods. On-therapy survivorship analyses revealed that patients with cardiac symptoms before β-blockers (n=598) 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 β-blocker therapy compared with asymptomatic patients; 32% of these symptomatic patients will have another cardiac event within 5 years while on prescribed β-blockers. Patients with a history of aborted cardiac arrest before starting β-blockers (n=113) had a hazard ratio of 12.9 (95% CI, 4.7 to 35.5) for aborted cardiac arrest or death while on prescribed β-blockers compared with asymptomatic patients; 14% of these patients will have another arrest (aborted or fatal) within 5 years on β-blockers.

Conclusions—β-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 β-blockers, particularly in those who were symptomatic before starting this therapy.