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An International Multicenter Cohort Study on β-Blockers for the Treatment of Symptomatic Children With Catecholaminergic Polymorphic Ventricular Tachycardia
PJ. Peltenburg, D. Kallas, JM. Bos, KVV. Lieve, S. Franciosi, TM. Roston, I. Denjoy, KB. Sorensen, S. Ohno, F. Roses-Noguer, T. Aiba, A. Maltret, MJ. LaPage, J. Atallah, JR. Giudicessi, SB. Clur, NA. Blom, M. Tanck, F. Extramiana, K. Kato, J....
Language English Country United States
Document type Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't
Grant support
RN380020–406814
Canadian Institute of Health Research
NLK
Free Medical Journals
from 1950 to 1 year ago
Open Access Digital Library
from 1950-01-01
Open Access Digital Library
from 1950-01-01
- MeSH
- Adrenergic beta-Antagonists pharmacology therapeutic use MeSH
- Child MeSH
- Cohort Studies MeSH
- Tachycardia, Ventricular drug therapy MeSH
- Humans MeSH
- Adolescent MeSH
- Check Tag
- Child MeSH
- Humans MeSH
- Adolescent MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
- Research Support, Non-U.S. Gov't MeSH
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.
1 D S A B C N A B F E J B G S B J T H P J S F D T R 5 B A L C v d W A A M W )
Cardiology Service Hospital Josep Trueta Girona Spain
Cardiovascular Genetics Center Institut d'Investigació Biomèdica Girona
Center for Biomedical Network Research on Cardiovascular Diseases
Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares
Department of Bioscience and Genetics National Cerebral and Cardiovascular Centre Suita Japan
Department of Cardiology Hospital Universitario y Politécnico La Fe Valencia Spain
Department of Cardiology Rigshospitalet Copenhagen Denmark
Department of Cardiology Royal Brompton Hospital London UK
Department of Cardiology University of Groningen University Medical Centre Groningen The Netherlands
Department of Cardiovascular Diseases University Hospitals Leuven Belgium
Department of Cardiovascular Medicine Graduate School of Medicine Nippon Medical School Tokyo Japan
Department of Cardiovascular Sciences University of Leuven Belgium
Department of Forensic Medicine Faculty of Medical Sciences University of Copenhagen Denmark
Department of Medicine University Medical Center Mannheim Germany
Department of Paediatrics Child and Youth Health The University of Auckland New Zealand
Department of Pediatric Cardiology Erasmus MC Sophia Rotterdam The Netherlands
Department of Pediatrics Division of Cardiology
Faculty of Medicine and Health The University of Sydney Australia
German Center for Cardiovascular Research
Heart and Lung Centre Helsinki University Hospital and Helsinki University Finland
Istituto Auxologico Italiano IRCCS Center for Cardiac Arrhythmias of Genetic Origin Milan Italy
LIRYC Institute Bordeaux University Hospital Bordeaux University France
Medical Science Department School of Medicine Universitat de Girona Spain
Medical Science Department School of Medicine University of Girona Spain
Motol University Hospital Prague Czech Republic
Murdoch Children's Research Institute and Department of Paediatrics Melbourne University Australia
The Royal Children's Hospital Melbourne Australia
Université de Nantes CHU Nantes CNRS INSERM l'institut du thorax France
Université de Nantes CNRS INSERM l'institut du thorax Nantes France
References provided by Crossref.org
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- $a An International Multicenter Cohort Study on β-Blockers for the Treatment of Symptomatic Children With Catecholaminergic Polymorphic Ventricular Tachycardia / $c PJ. Peltenburg, D. Kallas, JM. Bos, KVV. Lieve, S. Franciosi, TM. Roston, I. Denjoy, KB. Sorensen, S. Ohno, F. Roses-Noguer, T. Aiba, A. Maltret, MJ. LaPage, J. Atallah, JR. Giudicessi, SB. Clur, NA. Blom, M. Tanck, F. Extramiana, K. Kato, J. Barc, M. Borggrefe, ER. Behr, G. Sarquella-Brugada, J. Tfelt-Hansen, E. Zorio, H. Swan, JAE. Kammeraad, AD. Krahn, A. Davis, F. Sacher, PJ. Schwartz, JD. Roberts, JR. Skinner, MP. van den Berg, PJ. Kannankeril, F. Drago, T. Robyns, K. Haugaa, T. Tavacova, C. Semsarian, J. Till, V. Probst, R. Brugada, W. Shimizu, M. Horie, A. Leenhardt, MJ. Ackerman, S. Sanatani, C. van der Werf, AAM. Wilde
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- $a 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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