An International Multicenter Cohort Study on β-Blockers for the Treatment of Symptomatic Children With Catecholaminergic Polymorphic Ventricular Tachycardia. Issue 5 (1st February 2022)

• Record Type: Journal Article
• 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.;
• Is Part Of: Circulation. Volume 145:Issue 5(2022)
• Publication Date: 2022-02-01
• Subjects: atenolol -- child -- death, sudden, cardiac -- metoprolol -- nadolol -- polymorphic catecholergic ventricular tachycardia -- propranolol; Blood -- Circulation -- Periodicals; Cardiovascular system -- Periodicals; Cardiology -- Periodicals; Heart -- Diseases -- Periodicals; Blood Circulation; Cardiovascular System; Vascular Diseases; 616.1
• DOI: 10.1161/CIRCULATIONAHA.121.056018
• Languages: English
• ISSNs: 0009-7322

Abstract

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. Abstract : Supplemental Digital Content is available in the text.