Not All Beta-Blockers Are Equal in the Management of Long QT Syndrome Types 1 and 2

被引：216

作者：

Chockalingam, Priya ^{[1
,2
]}

Crotti, Lia ^{[3
,5
]}

Girardengo, Giulia ^{[3
]}

Johnson, Jonathan N. ^{[6
,7
,8
,9
,10
,11
,12
]}

Harris, Katy M. ^{[6
,7
,8
,9
,11
,12
]}

van der Heijden, Jeroen F. ^{[13
]}

Hauer, Richard N. W. ^{[13
]}

Beckmann, Britt M. ^{[14
]}

Spazzolini, Carla ^{[3
]}

Rordorf, Roberto ^{[4
]}

Rydberg, Annika ^{[15
]}

Clur, Sally-Ann B. ^{[2
]}

Fischer, Markus ^{[16
]}

van den Heuvel, Freek ^{[17
]}

Kaeaeb, Stefan ^{[14
]}

Blom, Nico A. ^{[2
,18
]}

Ackerman, Michael J. ^{[6
,7
,8
,9
,10
,11
,12
]}

Schwartz, Peter J. ^{[3
,19
,20
]}

Wilde, Arthur A. M. ^{[1
]}

机构：

[1] Univ Amsterdam, Acad Med Ctr, Dept Cardiol, Heart Failure Res Ctr, NL-1105 AZ Amsterdam, Netherlands

[2] Emma Childrens Hosp, Acad Med Ctr, Dept Pediat Cardiol, Amsterdam, Netherlands

[3] Univ Pavia, Dept Mol Med, I-27100 Pavia, Italy

[4] Fdn IRCCS Policlin S Matteo, Dept Cardiol, Pavia, Italy

[5] Helmholtz Zentrum, Inst Human Genet, Munich, Germany

[6] Mayo Clin, Windland Smith Rice Sudden Death Genom Lab, Rochester, MN USA

[7] Mayo Clin, Dept Med, Div Cardiovasc Dis, Rochester, MN USA

[8] Mayo Clin, Dept Med, Div Pediat Cardiol, Rochester, MN USA

[9] Mayo Clin, Dept Pediat, Div Pediat Cardiol, Rochester, MN USA

[10] Mayo Clin, Dept Pediat, Div Cardiovasc Dis, Rochester, MN USA

[11] Mayo Clin, Dept Mol Pharmacol & Expt Therapeut, Div Cardiovasc Dis, Rochester, MN USA

[12] Mayo Clin, Dept Mol Pharmacol & Expt Therapeut, Div Pediat Cardiol, Rochester, MN USA

[13] Univ Med Ctr, Dept Cardiol, Utrecht, Netherlands

[14] Univ Munich, Klinikum Grosshadern, Dept Med 1, D-8000 Munich, Germany

[15] Umea Univ, Dept Clin Sci, Umea, Sweden

[16] Univ Heidelberg Hosp, Dept Pediat Cardiol, Heidelberg, Germany

[17] Univ Groningen, Beatrix Childrens Hosp, Univ Med Ctr Groningen, Dept Pediat Cardiol, Groningen, Netherlands

[18] Leiden Univ, Med Ctr, Dept Pediat Cardiol, Leiden, Netherlands

[19] Univ Cape Town, Dept Med, Hatter Inst Cardiovasc Res, Cardiovasc Genet Lab, ZA-7925 Cape Town, South Africa

[20] King Saud Univ, Coll Med, Dept Family & Community Med, Riyadh 11461, Saudi Arabia

来源：

JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY | 2012年 / 60卷 / 20期

基金：

美国国家卫生研究院;

关键词：

breakthrough cardiac events; congenital long QT syndrome; metoprolol; nadolol; propranolol; EFFICACY; PHENOTYPE; FAILURES; GENOTYPE; THERAPY; EVENTS; RISK;

D O I：

10.1016/j.jacc.2012.07.046

中图分类号：

R5 [内科学];

学科分类号：

100201 [内科学];

摘要：

Objectives The purpose of this study was to compare the efficacy of beta-blockers in congenital long QT syndrome (LQTS). Background Beta-blockers are the mainstay in managing LQTS. Studies comparing the efficacy of commonly used beta-blockers are lacking, and clinicians generally assume they are equally effective. Methods Electrocardiographic and clinical parameters of 382 LQT1/LQT2 patients initiated on propranolol (n = 134), metoprolol (n = 147), and nadolol (n = 101) were analyzed, excluding patients <1 year of age at beta-blocker initiation. Symptoms before therapy and the first breakthrough cardiac events (BCEs) were documented. Results Patients (56% female, 27% symptomatic, heart rate 76 +/- 16 beats/min, QTc 472 +/- 46 ms) were started on beta-blocker therapy at a median age of 14 years (interquartile range: 8 to 32 years). The QTc shortening with propranolol was significantly greater than with other beta-blockers in the total cohort and in the subset with QTc >480 ms. None of the asymptomatic patients had BCEs. Among symptomatic patients (n = 101), 15 had BCEs (all syncopes). The QTc shortening was significantly less pronounced among patients with BCEs. There was a greater risk of BCEs for symptomatic patients initiated on metoprolol compared to users of the other 2 beta-blockers combined, after adjustment for genotype (odds ratio: 3.95, 95% confidence interval: 1.2 to 13.1, p = 0.025). Kaplan-Meier analysis showed a significantly lower event-free survival for symptomatic patients receiving metoprolol compared to propranolol/nadolol. Conclusions Propranolol has a significantly better QTc shortening effect compared to metoprolol and nadolol, especially in patients with prolonged QTc. Propranolol and nadolol are equally effective, whereas symptomatic patients started on metoprolol are at a significantly higher risk for BCEs. Metoprolol should not be used for symptomatic LQT1 and LQT2 patients. (J Am Coll Cardiol 2012;60:2092-9) (C) 2012 by the American College of Cardiology Foundation

引用

页码：2092 / 2099

页数：8

共 18 条

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Molecular determinants of local anesthetic action of beta-blocking drugs: Implications for therapeutic management of long QT syndrome variant 3 [J].