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An International Multi-Center Cohort Study on β-blockers for the Treatment of Symptomatic Children with Catecholaminergic Polymorphic Ventricular Tachycardia


Circulation. 2021 Dec 7. doi: 10.1161/CIRCULATIONAHA.121.056018. Online ahead of print.

ABSTRACT

Background: Symptomatic children with catecholaminergic polymorphic ventricular tachycardia (CPVT) are at risk for recurrent arrhythmic events. Beta-blockers (BBs) decrease this risk, but studies comparing individual BBs in sizeable cohorts are lacking. We aimed to assess the association between risk for arrhythmic events and type of BB in a large cohort of symptomatic children with CPVT. Methods: From two international registries of patients with CPVT, RYR2 variant-carrying symptomatic children (defined as syncope or sudden cardiac arrest prior to BB initiation and age at start of BB therapy <18 years), treated with a BB were included. Cox-regression analyses with time-dependent covariates for BB 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 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 non-selective BB (predominantly nadolol [n=140] or propranolol [n=70]) and 111 (33.7%) used a β1-selective BB (predominantly atenolol [n=51], metoprolol [n=33], or bisoprolol [n=19]) as initial BB. Baseline characteristics did not differ. The HR for both the primary and secondary outcomes were higher for β1-selective compared with non-selective BBs (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: B1-selective BBs were associated with a significantly higher risk for arrhythmic events in symptomatic children with CPVT compared with non-selective BBs, specifically nadolol. Nadolol, or propranolol if nadolol is unavailable, should be the preferred BB for treating symptomatic children with CPVT.

PMID:34874747 | DOI:10.1161/CIRCULATIONAHA.121.056018

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