An International Multicenter Cohort Study on β-Blockers for the Treatment of Symptomatic Children With Catecholaminergic Polymorphic Ventricular Tachycardia

An International Multicenter Cohort Study on β-Blockers for the Treatment of Symptomatic Children With Catecholaminergic Polymorphic Ventricular Tachycardia.

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Item Type: Article
Official URL: https://doi.org/10.1161/CIRCULATIONAHA.121.056018
Journal or Publication Title: Circulation
Volume: 145
Number: 5
Page Range: pp. 333-344
Date: 7 December 2021
Divisions: Molecular Cardiology
Depositing User: General Admin
Identification Number: 10.1161/CIRCULATIONAHA.121.056018
ISSN: 0009-7322
Date Deposited: 08 Jan 2023 23:12
Abstract:

Background: Symptomatic children with catecholaminergic polymorphic ventricular tachycardia (CPVT) are at risk for recurrent arrhythmic events. β-Blockers decrease this risk, but studies comparing individual β-blockers in sizeable cohorts are lacking. We aimed to assess the association between risk for arrhythmic events and type of β-blocker in a large cohort of symptomatic children with CPVT.

Methods: From 2 international registries of patients with CPVT, RYR2 variant-carrying symptomatic children (defined as syncope or sudden cardiac arrest before β-blocker initiation and age at start of β-blocker therapy <18 years), treated with a β-blocker were included. Cox regression analyses with time-dependent covariates for β-blockers and potential confounders were used to assess the hazard ratio (HR). The primary outcome was the first occurrence of sudden cardiac death, sudden cardiac arrest, appropriate implantable cardioverter-defibrillator shock, or syncope. The secondary outcome was the first occurrence of any of the primary outcomes except syncope.

Results: We included 329 patients (median age at diagnosis, 12 [interquartile range, 7-15] years, 35% females). Ninety-nine (30.1%) patients experienced the primary outcome and 74 (22.5%) experienced the secondary outcome during a median follow-up of 6.7 (interquartile range, 2.8-12.5) years. Two-hundred sixteen patients (66.0%) used a nonselective β-blocker (predominantly nadolol [n=140] or propranolol [n=70]) and 111 (33.7%) used a β1-selective β-blocker (predominantly atenolol [n=51], metoprolol [n=33], or bisoprolol [n=19]) as initial β-blocker. Baseline characteristics did not differ. The HRs for both the primary and secondary outcomes were higher for β1-selective compared with nonselective β-blockers (HR, 2.04 [95% CI, 1.31-3.17]; and HR, 1.99 [95% CI, 1.20-3.30], respectively). When assessed separately, the HR for the primary outcome was higher for atenolol (HR, 2.68 [95% CI, 1.44-4.99]), bisoprolol (HR, 3.24 [95% CI, 1.47-7.18]), and metoprolol (HR, 2.18 [95% CI, 1.08-4.40]) compared with nadolol, but did not differ from propranolol. The HR of the secondary outcome was only higher in atenolol compared with nadolol (HR, 2.68 [95% CI, 1.30-5.55]).

Conclusions: β1-selective β-blockers were associated with a significantly higher risk for arrhythmic events in symptomatic children with CPVT compared with nonselective β-blockers, specifically nadolol. Nadolol, or propranolol if nadolol is unavailable, should be the preferred β-blocker for treating symptomatic children with CPVT.

Creators:
Creators
Email
Peltenburg, Puck J.
UNSPECIFIED
Kallas, Dania
UNSPECIFIED
Bos, Johan M.
UNSPECIFIED
Lieve, Krystien V.V.
UNSPECIFIED
Franciosi, Sonia
UNSPECIFIED
Roston, Thomas M.
UNSPECIFIED
Denjoy, Isabelle
UNSPECIFIED
Sorensen, Katrina B.
UNSPECIFIED
Ohno, Seiko
UNSPECIFIED
Roses-Noguer, Ferran
UNSPECIFIED
Aiba, Takeshi
UNSPECIFIED
Maltret, Alice
UNSPECIFIED
LaPage, Martin J.
UNSPECIFIED
Atallah, Joseph
UNSPECIFIED
Giudicessi, John R.
UNSPECIFIED
Clur, Sally-Ann B.
UNSPECIFIED
Blom, Nico A.
UNSPECIFIED
Tanck, Michael
UNSPECIFIED
Extramiana, Fabrice
UNSPECIFIED
Kato, Koichi
UNSPECIFIED
Barc, Julien
UNSPECIFIED
Borggrefe, Martin
UNSPECIFIED
Behr, Elijah R.
UNSPECIFIED
Sarquella-Brugada, Georgia
UNSPECIFIED
Tfelt-Hansen, Jacob
UNSPECIFIED
Zorio, Esther
UNSPECIFIED
Swan, Heikki
UNSPECIFIED
Kammeraad, Janneke A.E.
UNSPECIFIED
Krahn, Andrew D.
UNSPECIFIED
Davis, Andrew
UNSPECIFIED
Sacher, Frederic
UNSPECIFIED
Schwartz, Peter J.
UNSPECIFIED
Roberts, Jason D.
UNSPECIFIED
Skinner, Jonathan R.
UNSPECIFIED
van den Berg, Maarten P.
UNSPECIFIED
Kannankeril, Prince J.
UNSPECIFIED
Drago, Fabrizio
UNSPECIFIED
Robyns, Tomas
UNSPECIFIED
Haugaa, Kristina
UNSPECIFIED
Tavacova, Terezia
UNSPECIFIED
Semsarian, Christopher
UNSPECIFIED
Till, Jan
UNSPECIFIED
Probst, Vincent
UNSPECIFIED
Brugada, Ramon
UNSPECIFIED
Shimizu, Wataru
UNSPECIFIED
Horie, Minoru
UNSPECIFIED
Leenhardt, Antoine
UNSPECIFIED
Ackerman, Michael J.
UNSPECIFIED
Sanatani, Shubhayan
UNSPECIFIED
van der Werf, Christian
UNSPECIFIED
Wilde, Arthur A.M.
UNSPECIFIED
Last Modified: 08 Jan 2023 23:12
URI: https://eprints.centenary.org.au/id/eprint/1352

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