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

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

28 Citations (Scopus)
31 Downloads (Pure)


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
Pages (from-to)333-344
Number of pages12
Issue number5
Publication statusPublished - 1 Feb 2022

Bibliographical note

Funding Information:
This work was supported by eRare (E-rare 3 - Joint Call 2015 to dr. Wilde, dr. Leenhardt, and dr. Sanatani), the Netherlands CardioVascular Research Initiative: the Dutch Heart Foundation, Dutch Federation of University Medical Centres, the Netherlands Organisation for Health Research and Development and the Royal Netherlands Academy of Sciences (PREDICT2 to Dr Wilde), the ZonMW Priority Medicines for Rare Diseases and Orphan Drugs (grant 113304045 to Dr Van der Werf), the Mayo Clinic Windland Smith Rice Comprehensive Sudden Cardiac Death Program (to Dr Ackerman), the AEPC junior members research grant 2019 (to Dr Peltenburg), Heart and Stroke Foundation (G-19-0024239 and G-15-0008870 to Dr Sanatani), the Heart in Rhythm Organization (Dr Krahn, Principal Investigator) that receives support from the Canadian Institute of Health Research (RN380020–406814), National Health and Medical Research Council Practitioner Fellowship (No. 1154992, to Dr Semsarian), Instituto de Salud Carlos III and FEDER Union Europea, Una forma de hacer Europa (PT17/0015/0043 to La Fe Biobank to Dr Zorio), Memorial Nacho Barberá (crowd funding, to Dr Zorio) and Agènce Nationale de la Recherche (ANR-19-CE14-0031-001, to Dr Zorio), Supported by Ministry of Health, Czech Republic: conceptual development of research organization, Motol Univesity Hospital, Prague, Czech Republic (00064203 to Dr. Tavacova), The Robert Lancaster Memorial Fund (to Dr Behr), and the German Center for Cardiovascular Research (to Dr Borggrefe), and the Japan Agency for Medical Research and Development (JP18ek0109202 to Dr Ohno).

Publisher Copyright:
© 2022 Lippincott Williams and Wilkins. All rights reserved.


Dive into the research topics of 'An International Multicenter Cohort Study on β-Blockers for the Treatment of Symptomatic Children With Catecholaminergic Polymorphic Ventricular Tachycardia'. Together they form a unique fingerprint.

Cite this