102-06: Risk of Life-Threatening Cardiac Events in Some Long QT Syndrome Patients Treated with β-Blockers

Abstract

Introduction: β-blockers (BB) are currently the mainstay of long QT syndrome (LQTS) treatment. Previous studies showed that some patients will still experience cardiac events on BB treatment. However, data regarding the risk of life-threatening cardiac events (LTCE) while on BB treatment and the association between clinical and genetic factors and BB treatment failure are currently not available. Methods: The study population comprised 1719 BB-treated LQTS patients (86% genotyped positive) from the Rochester New York registry. Patients were included if they had no aborted cardiac arrest (ACA) or implantable cardioverter defibrillator (ICD) prior to treatment initiation. Follow up started at the day of BB initiation and patients were censored when they stopped taking BB, at the day of ICD implantation or at the age of 50. The combined endpoint of LTCE was defined as ACA or LQTS-related death. Results: During a mean ± SD follow-up time of 7.66 ± 6.95 years the crude LCTE rate was 4%. The risk of LTCE was associated with QTc ≥ 500 msec (HR = 1.72, CI 1.05-2.82, p = 0.032), males <13 years vs. males ≥ 13 years (HR = 4.27, CI 1.00-18.25, p = 0.05), syncope prior to BB initiation (HR = 1.94, CI = 1.10-3.42, p = 0.021), time-dependent syncope (after BB initiation) (HR = 3.98, CI 2.24-7.07, p < 0.001), LQT3 vs. LQT1 genotype (HR = 8.70, CI 2.03-37.36, p = 0.004) and LQT2 vs. LQT1 genotype (HR = 3.17, CI 1.03-9.70, p = 0.044). Conclusions: Among BB-treated LQTS patients, syncope prior the BB initiation, QTc ≥ 500 msec, syncope on BB treatment, LQT3 and LQT2 genotypes were associated with increased risk of LTCE compared to LQT1 patients, while older males were at lower risk. Clearly there is the need for more effective drug and device therapy in these high-risk patients who are not adequately protected by BB-therapy alone.