Background: Beta-blocker efficacy in long-QT syndrome type 1 is good but variably reported, and the causes of cardiac events despite beta-blocker therapy have not been ascertained.
Methods and results: This was a retrospective study of the details surrounding cardiac events in 216 genotyped long-QT syndrome type 1 patients treated with beta-blocker and followed up for a median time of 10 years. Before beta-blocker, cardiac events occurred in 157 patients (73%) at a median age of 9 years, with cardiac arrest (CA) in 26 (12%). QT-prolonging drugs were used by 17 patients; 9 of 17 (53%) had CA compared with 17 of 199 nonusers (8.5%; odds ratio, 12.0; 95% confidence interval, 4.1 to 35.3; P<0.001). After beta-blocker, 75% were asymptomatic, and cardiac events were significantly reduced (P<0.001), with a median event count (quartile 1 to 3) per person of 0 (0 to 1). Twelve patients (5.5%) suffered CA/sudden death, but 11 of 12 (92%) were noncompliant (n=8), were on a QT-prolonging drug (n=2), or both (n=1) at the time of the event. The risk for CA/sudden death in compliant patients not taking QT-prolonging drugs was dramatically less compared with noncompliant patients on QT-prolonging drugs (odds ratio, 0.03; 95% confidence interval, 0.003 to 0.22; P=0.001). None of the 26 patients with CA before beta-blocker had CA/sudden death on beta-blockers.
Conclusions: beta-Blockers are extremely effective in long-QT syndrome type 1 and should be administered at diagnosis and ideally before the preteen years. beta-Blocker noncompliance and use of QT-prolonging drug are responsible for almost all life-threatening "beta-blocker failures." beta-Blockers are appropriate therapy for asymptomatic patients and those who have never had a CA or beta-blocker therapy. Routine implantation of cardiac defibrillators in such patients does not appear justified.