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Association of Long QT Syndrome Loci and Cardiac Events Among Patients Treated With -Blockers

Silvia G. Priori, MD, PhD; Carlo Napolitano, MD, PhD; Peter J. Schwartz, MD; Massimiliano Grillo, MD; Raffaella Bloise, MD; Elena Ronchetti, PhD; Cinzia Moncalvo, MD; Chiara Tulipani, MD; Alessia Veia, MD; Georgia Bottelli, BS; Janni Nastoli, BS

JAMA. 2004;292:1341-1344.

Context  Data on the efficacy of -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 -blocker–treated LQTS patients.

Design, Setting, and Patients  Consecutive LQTS-genotyped patients (n = 335) in Italy treated with -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 -blocker therapy according to genotype.

Results  Cardiac events among patients receiving -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 -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 -blockers, there is a high rate of cardiac events, particularly among patients with LQT2 and LQT3 genotypes.

Author Affiliations: Molecular Cardiology, IRCCS Fondazione Maugeri (Drs Priori, Napolitano, Grillo, Bloise, Ronchetti, Moncalvo, Tulipani, and Veia and Mss Bottelli and Nastoli); Department of Cardiology, IRCCS Policlinico S. Matteo (Dr Schwartz); and University of Pavia (Drs Priori and Schwartz), Pavia, Italy.

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