CONTEXT:

Data on the efficacy of beta-blockers in the 3 most common genetic long QT syndrome (LQTS) loci are limited.

OBJECTIVE:

To describe and assess outcome in a large systematically genotyped population of beta-blocker-treated LQTS patients.

DESIGN, SETTING, AND PATIENTS:

Consecutive LQTS-genotyped patients (n = 335) in Italy treated with beta-blockers for an average of 5 years.

MAIN OUTCOME MEASURES:

Cardiac events (syncope, ventricular tachycardia/torsades de pointes, cardiac arrest, and sudden cardiac death) while patients received beta-blocker therapy according to genotype.

RESULTS:

Cardiac events among patients receiving beta-blocker therapy occurred in 19 of 187 (10%) LQT1 patients, 27 of 120 (23%) LQT2 patients, and 9 of 28 (32%) LQT3 patients (P<.001). The risk of cardiac events was higher among LQT2 (adjusted relative risk, 2.81; 95% confidence interval [CI], 1.50-5.27; P =.001) and LQT3 (adjusted relative risk, 4.00; 95% CI, 2.45-8.03; P<.001) patients than among LQT1 patients, suggesting inadequate protection from beta-blocker therapy. Other important predictors of risk were a QT interval corrected for heart rate that was more than 500 ms in patients receiving therapy (adjusted relative risk, 2.01; 95% CI, 1.16-3.51; P =.01) and occurrence of a first cardiac event before the age of 7 years (adjusted RR, 4.34; 95% CI, 2.35-8.03; P<.001).

CONCLUSION:

Among patients with genetic LQTS treated with beta-blockers, there is a high rate of cardiac events, particularly among patients with LQT2 and LQT3 genotypes.