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

Puck J. Peltenburg, Dania Kallas, Johan M. Bos, Krystien V.V. Lieve, Sonia Franciosi, Thomas M. Roston, Isabelle Denjoy, Katrina B. Sorensen, Seiko Ohno, Ferran Roses-Noguer, Takeshi Aiba, Alice Maltret, Martin J. Lapage, Joseph Atallah, John R. Giudicessi, Sally Ann B. Clur, Nico A. Blom, Michael Tanck, Fabrice Extramiana, Koichi KatoJulien Barc, Martin Borggrefe, Elijah R. Behr, Georgia Sarquella-Brugada, Jacob Tfelt-Hansen, Esther Zorio, Heikki Swan, Janneke A.E. Kammeraad, Andrew D. Krahn, Andrew Davis, Frederic Sacher, Peter J. Schwartz, Jason D. Roberts, Jonathan R. Skinner, Maarten P. Van Den Berg, Prince J. Kannankeril, Fabrizio Drago, Tomas Robyns, Kristina Haugaa, Terezia Tavacova, Christopher Semsarian, Jan Till, Vincent Probst, Ramon Brugada, Wataru Shimizu, Minoru Horie, Antoine Leenhardt, Michael J. Ackerman, Shubhayan Sanatani, Christian Van Der Werf, Arthur A.M. Wilde

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
Pages (from-to)333-344
Number of pages12
Issue number5
StatePublished - Feb 1 2022


  • atenolol
  • child
  • death, sudden, cardiac
  • metoprolol
  • nadolol
  • polymorphic catecholergic ventricular tachycardia
  • propranolol

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)


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