Background: Beta-blockers are the mainstay therapy in patients with the congenital long-QT syndrome (LQTS) types 1 and 2. However, limited data exist regarding the efficacy and limitations of this form of medical management within high-risk subsets of these populations.
Methods and results: Multivariate analysis was carried out to identify age-related gender- and genotype-specific risk factors for cardiac events (comprising syncope, aborted cardiac arrest [ACA] or sudden cardiac death [SCD]) from birth through age 40 years among 971 LQT1 (n = 549) and LQT2 (n = 422) patients from the International LQTS Registry. Risk factors for cardiac events included the LQT1 genotype (HR = 1.49, P = 0.003) and male gender (HR = 1.31, P = 0.04) in the 0-14 years age group; and the LQT2 genotype (HR = 1.67, P < 0.001) and female gender (HR = 2.58, P < 0.001) in the 15-40 years age group. Gender-genotype subset analysis showed enhanced risk among LQT1 males (HR = 1.93, P < 0.001) and LQT2 females (HR = 3.28, P < 0.001) in the 2 respective age groups. Beta-blocker therapy was associated with a significant risk-reduction in high-risk patients, including a 67% reduction (P = 0.02) in LQT1 males and a 71% reduction (P < 0.001) in LQT2 females. Life-threatening events (ACA/SCD) rarely occurred as a presenting symptom among beta-blocker-treated patients. However, high-risk patients who experienced syncope during beta-blocker therapy had a relatively high rate of subsequent ACA/SCD (>1 event per 100 patient-years).
Conclusions: The present findings suggest that beta-blocker therapy should be routinely administered to all high-risk LQT1 and LQT2 patients without contraindications as a first line measure, whereas primary defibrillator therapy should be recommended for those who experience syncope during medical therapy.