An International Multicenter Cohort Study on β-Blockers for the Treatment of Symptomatic Children With Catecholaminergic Polymorphic Ventricular Tachycardia
Authors: Peltenburg Puck J. , Kallas Dania , Bos Johan M. , Lieve Krystien V.V. , Franciosi Sonia , Roston Thomas M. , Denjoy Isabelle , Sorensen Katrina B. , Ohno Seiko , Roses-Noguer Ferran , Aiba Takeshi , Maltret Alice , LaPage Martin J. , Atallah Joseph , Giudicessi John R. , Clur Sally-Ann B. , Blom Nico A. , Tanck Michael , Extramiana Fabrice , Kato Koichi , Barc Julien , Borggrefe Martin , Behr Elijah R. , Sarquella-Brugada Georgia , Tfelt-Hansen Jacob , Zorio Esther , Swan Heikki , Kammeraad Janneke A.E. , Krahn Andrew D. , Davis Andrew , Sacher Frederic , Schwartz Peter J. , Roberts Jason D. , Skinner Jonathan R. , van den Berg Maarten P. , Kannankeril Prince J. , Drago Fabrizio , Robyns Tomas , Haugaa Kristina , Tavacova Terezia , Semsarian Christopher , Till Jan , Probst Vincent , Brugada Ramon , Shimizu Wataru , Horie Minoru , Leenhardt Antoine , Ackerman Michael J. , Sanatani Shubhayan , van der Werf Christian , Wilde Arthur A.M. 
Published: December 2021

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.