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(Circulation. 2009;119:215-221.)
© 2009 American Heart Association, Inc.

Arrhythmia/Electrophysiology

High Efficacy of β-Blockers in Long-QT Syndrome Type 1

Contribution of Noncompliance and QT-Prolonging Drugs to the Occurrence of β-Blocker Treatment "Failures"

G. Michael Vincent, MD; Peter J. Schwartz, MD; Isabelle Denjoy, MD; Heikki Swan, MD; Candice Bithell, BA; Carla Spazzolini, DVM, MS; Lia Crotti, MD, PhD; Kirsi Piippo, MD; Jean-Marc Lupoglazoff, MD, PhD; Elizabeth Villain, MD; Silvia G. Priori, MD, PhD; Carlo Napolitano, MD, PhD; Li Zhang, MD

From the Departments of Medicine, LDS Hospital and University of Utah, Salt Lake City (G.M.V., C.B., L.Z.); Department of Cardiology, IRCCS Fondazione Policlinico S. Matteo (P.J.S., C.S., L.C.) and University of Pavia (P.J.S., S.G.P.), Pavia, Italy; Laboratory of Cardiovascular Genetics, IRCCS Instituto Auxologico, Milan, Italy (P.J.S.); Cardiovascular Genetics Laboratory, Hatter Institute for Cardiovascular Research, Department of Medicine, University of Cape Town, South Africa (P.J.S.); Service de Cardiologie, Hôpital Lariboisière, Paris, France (I.D.); Departments of Cardiology (H.S.) and Medicine (K.P.), Helsinki University, Helsinki, Finland; Hôpital Robert-Debré, Paris, France (J.-M.L.); Hôpital Necker Enfant Maladies, Paris, France (E.V.); and Molecular Cardiology, IRCCS Fondazione S. Maugeri, Pavia, Italy (S.G.P., C.N.).

Correspondence to G. Michael Vincent, MD, 324 10th Ave, Suite 127, Salt Lake City, UT 84103. E-mail g.michael.vincent{at}intermountainmail.org

Received February 11, 2008; accepted October 6, 2008.

Background— β-Blocker efficacy in long-QT syndrome type 1 is good but variably reported, and the causes of cardiac events despite β-blocker therapy have not been ascertained.

Methods and Results— This was a retrospective study of the details surrounding cardiac events in 216 genotyped long-QT syndrome type 1 patients treated with β-blocker and followed up for a median time of 10 years. Before β-blocker, cardiac events occurred in 157 patients (73%) at a median age of 9 years, with cardiac arrest (CA) in 26 (12%). QT-prolonging drugs were used by 17 patients; 9 of 17 (53%) had CA compared with 17 of 199 nonusers (8.5%; odds ratio, 12.0; 95% confidence interval, 4.1 to 35.3; P<0.001). After β-blocker, 75% were asymptomatic, and cardiac events were significantly reduced (P<0.001), with a median event count (quartile 1 to 3) per person of 0 (0 to 1). Twelve patients (5.5%) suffered CA/sudden death, but 11 of 12 (92%) were noncompliant (n=8), were on a QT-prolonging drug (n=2), or both (n=1) at the time of the event. The risk for CA/sudden death in compliant patients not taking QT-prolonging drugs was dramatically less compared with noncompliant patients on QT-prolonging drugs (odds ratio, 0.03; 95% confidence interval, 0.003 to 0.22; P=0.001). None of the 26 patients with CA before β-blocker had CA/sudden death on β-blockers.

Conclusions— β-Blockers are extremely effective in long-QT syndrome type 1 and should be administered at diagnosis and ideally before the preteen years. β-Blocker noncompliance and use of QT-prolonging drug are responsible for almost all life-threatening "β-blocker failures." β-Blockers are appropriate therapy for asymptomatic patients and those who have never had a CA or β-blocker therapy. Routine implantation of cardiac defibrillators in such patients does not appear justified.

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