Risk of Cardiac Events in Patients With Asthma and Long-QT Syndrome Treated With Beta₂ Agonists

The clinical course and risk factors associated with β₂-agonist therapy for asthma have not been investigated previously in patients with the long-QT syndrome (LQTS). The risk of a first LQTS-related cardiac event due to β₂-agonist therapy was examined in 3,287 patients enrolled in the International LQTS Registry with QTc ≥450 ms. The Cox proportional hazards model was used to assess the independent contribution of clinical factors for first cardiac events (syncope, aborted cardiac arrest, or sudden death) from birth through age 40. Time-dependent β₂-agonist therapy for asthma was associated with an increased risk for cardiac events (hazard ratio [HR] = 2.00, 95% confidence interval 1.26 to 3.15, p = 0.003) after adjustment for relevant covariates including time-dependent β-blocker use, gender, QTc, and history of asthma. This risk was augmented within the first year after the initiation of β₂-agonist therapy (HR = 3.53, p = 0.006). The combined use of β₂-agonist therapy and anti-inflammatory steroids was associated with an elevated risk for cardiac events (HR = 3.66, p <0.01); β-blocker therapy was associated with a reduction in cardiac events in those using β₂ agonists (HR = 0.14, p = 0.05). In conclusion, β₂-agonist therapy was associated with an increased risk for cardiac events in patients with asthma with LQTS, and this risk was diminished in patients receiving β blockers.