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Published on: December 22, 2023
An International Multicenter Cohort Study on β-Blockers for the Treatment of Symptomatic Children With
Puck J Peltenburg1,2, Dania Kallas3, Johan M Bos4
1Amsterdam UMC, University of Amsterdam, Heart Centre, Department of Clinical and Experimental Cardiology, Amsterdam Cardiovascular Sciences, The Netherlands (P.J.P., K.V.V.L., M.T., C.v.d.W., A.A.M.W.).
Insights
Nonselective beta-blockers like nadolol are more effective than beta1-selective agents in preventing dangerous heart events in children with catecholaminergic polymorphic ventricular tachycardia (CPVT). Nadolol or propranolol should be the preferred treatment for these young patients.
Area of Science:
- Cardiology
- Pediatric Electrophysiology
- Pharmacology
Background:
- Symptomatic children with catecholaminergic polymorphic ventricular tachycardia (CPVT) face a high risk of recurrent life-threatening arrhythmic events.
- While beta-blockers are standard treatment, evidence comparing the efficacy of individual agents in large pediatric cohorts is limited.
- This study addresses the need for comparative data on beta-blocker effectiveness in pediatric CPVT management.
Purpose of the Study:
- To evaluate the association between different types of beta-blockers and the risk of arrhythmic events in symptomatic children diagnosed with CPVT.
- To compare the effectiveness of nonselective versus beta1-selective beta-blockers in preventing adverse cardiac outcomes in this pediatric population.
Main Methods:
- Analysis of data from two international CPVT patient registries, including symptomatic children with RYR2 variants initiating beta-blocker therapy before age 18.
- Cox regression models with time-dependent covariates were employed to determine hazard ratios (HR) for primary (sudden cardiac death, cardiac arrest, appropriate ICD shock, syncope) and secondary outcomes (excluding syncope).
- Patients were categorized based on their initial beta-blocker: nonselective (nadolol, propranolol) or beta1-selective (atenolol, metoprolol, bisoprolol).
Main Results:
- The study included 329 children, with 30.1% experiencing the primary outcome and 22.5% the secondary outcome during a median follow-up of 6.7 years.
- Beta1-selective beta-blockers were associated with significantly higher risks for both primary (HR, 2.04) and secondary outcomes (HR, 1.99) compared to nonselective agents.
- Nadolol demonstrated a lower risk compared to atenolol, bisoprolol, and metoprolol for the primary outcome, while propranolol showed no significant difference from beta1-selective agents.
Conclusions:
- Beta1-selective beta-blockers are linked to an increased risk of arrhythmic events in symptomatic children with CPVT compared to nonselective beta-blockers.
- Nadolol is identified as a preferred beta-blocker, with propranolol as a viable alternative if nadolol is unavailable, for managing pediatric CPVT.
- These findings support the use of nonselective beta-blockers, particularly nadolol, for improved risk management in children with CPVT.
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.
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