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