{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T13:42:21Z","timestamp":1790948541092,"version":"4.1.0"},"reference-count":28,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2022,2]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Symptomatic children with catecholaminergic polymorphic ventricular tachycardia (CPVT) are at risk for recurrent arrhythmic events. \u03b2-Blockers decrease this risk, but studies comparing individual \u03b2-blockers in sizeable cohorts are lacking. We aimed to assess the association between risk for arrhythmic events and type of \u03b2-blocker in a large cohort of symptomatic children with CPVT.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>\n                      From 2 international registries of patients with CPVT,\n                      <jats:italic>RYR2<\/jats:italic>\n                      variant\u2013carrying symptomatic children (defined as syncope or sudden cardiac arrest before \u03b2-blocker initiation and age at start of \u03b2-blocker therapy &lt;18 years), treated with a \u03b2-blocker were included. Cox regression analyses with time-dependent covariates for \u03b2-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.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>We included 329 patients (median age at diagnosis, 12 [interquartile range, 7\u201315] 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\u201312.5) years. Two-hundred sixteen patients (66.0%) used a nonselective \u03b2-blocker (predominantly nadolol [n=140] or propranolol [n=70]) and 111 (33.7%) used a \u03b21-selective \u03b2-blocker (predominantly atenolol [n=51], metoprolol [n=33], or bisoprolol [n=19]) as initial \u03b2-blocker. Baseline characteristics did not differ. The HRs for both the primary and secondary outcomes were higher for \u03b21-selective compared with nonselective \u03b2-blockers (HR, 2.04 [95% CI, 1.31\u20133.17]; and HR, 1.99 [95% CI, 1.20\u20133.30], respectively). When assessed separately, the HR for the primary outcome was higher for atenolol (HR, 2.68 [95% CI, 1.44\u20134.99]), bisoprolol (HR, 3.24 [95% CI, 1.47\u20137.18]), and metoprolol (HR, 2.18 [95% CI, 1.08\u20134.40]) 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\u20135.55]).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>\u03b21-selective \u03b2-blockers were associated with a significantly higher risk for arrhythmic events in symptomatic children with CPVT compared with nonselective \u03b2-blockers, specifically nadolol. Nadolol, or propranolol if nadolol is unavailable, should be the preferred \u03b2-blocker for treating symptomatic children with CPVT.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circulationaha.121.056018","type":"journal-article","created":{"date-parts":[[2021,12,7]],"date-time":"2021-12-07T16:18:46Z","timestamp":1638893926000},"page":"333-344","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":73,"title":["An International Multicenter Cohort Study on \u03b2-Blockers for the Treatment of Symptomatic Children With Catecholaminergic Polymorphic Ventricular Tachycardia"],"prefix":"10.1161","volume":"145","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8942-164X","authenticated-orcid":true,"given":"Puck J.","family":"Peltenburg","sequence":"first","affiliation":[{"name":"Amsterdam 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.)."},{"name":"Department of Pediatric Cardiology, Emma Children\u2019s Hospital, Amsterdam UMC, University of Amsterdam, The Netherlands (P.J.P., S.-A.B.C., N.A.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dania","family":"Kallas","sequence":"additional","affiliation":[{"name":"BC Children\u2019s Hospital, Vancouver, Canada. Department of Pediatrics (D.K., S.F., T.M.R., S.S.), University of British Columbia, Vancouver, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3635-2003","authenticated-orcid":true,"given":"Johan M.","family":"Bos","sequence":"additional","affiliation":[{"name":"Departments of Cardiovascular Medicine, Pediatric and Adolescent Medicine, and Molecular Pharmacology &amp; Experimental Therapeutics, Division of Heart Rhythm Services and Pediatric Cardiology, Windland Smith Rice Sudden Death Genomics Laboratory, Mayo Clinic, Rochester, MN (J.M.B., K.B.S., J.R.G., M.J.A.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krystien V.V.","family":"Lieve","sequence":"additional","affiliation":[{"name":"Amsterdam 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.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonia","family":"Franciosi","sequence":"additional","affiliation":[{"name":"BC Children\u2019s Hospital, Vancouver, Canada. Department of Pediatrics (D.K., S.F., T.M.R., S.S.), University of British Columbia, Vancouver, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5663-4377","authenticated-orcid":true,"given":"Thomas M.","family":"Roston","sequence":"additional","affiliation":[{"name":"BC Children\u2019s Hospital, Vancouver, Canada. Department of Pediatrics (D.K., S.F., T.M.R., S.S.), University of British Columbia, Vancouver, Canada."},{"name":"Center for Cardiovascular Innovation, Division of Cardiology (T.M.R., A.D.K.), University of British Columbia, Vancouver, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1786-9461","authenticated-orcid":true,"given":"Isabelle","family":"Denjoy","sequence":"additional","affiliation":[{"name":"Member of the European Reference Network for rare, low prevalence and complex diseases of the heart: ERN GUARD-Heart (ERN GUARDHEART; I.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., V.B., A.L., C.v.d.W., A.A.M.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6087-0484","authenticated-orcid":true,"given":"Katrina B.","family":"Sorensen","sequence":"additional","affiliation":[{"name":"Departments of Cardiovascular Medicine, Pediatric and Adolescent Medicine, and Molecular Pharmacology &amp; Experimental Therapeutics, Division of Heart Rhythm Services and Pediatric Cardiology, Windland Smith Rice Sudden Death Genomics Laboratory, Mayo Clinic, Rochester, MN (J.M.B., K.B.S., J.R.G., M.J.A.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1209-8896","authenticated-orcid":true,"given":"Seiko","family":"Ohno","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Shiga University of Medical Science, Otsu, Japan (S.O., K.K., M.H.), National Cerebral and Cardiovascular Centre, Suita, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5955-7490","authenticated-orcid":true,"given":"Ferran","family":"Roses-Noguer","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Royal Brompton Hospital, London, UK (F.R.-N., J.T.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1779-7282","authenticated-orcid":true,"given":"Takeshi","family":"Aiba","sequence":"additional","affiliation":[{"name":"Department of Bioscience and Genetics (S.O.), Department of Cardiovascular Medicine (T.A., W.S.), National Cerebral and Cardiovascular Centre, Suita, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice","family":"Maltret","sequence":"additional","affiliation":[{"name":"Amsterdam 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.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5694-6570","authenticated-orcid":true,"given":"Martin J.","family":"LaPage","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Cardiology; University of Michigan, Ann Arbor (M.J.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8763-2067","authenticated-orcid":true,"given":"Joseph","family":"Atallah","sequence":"additional","affiliation":[{"name":"Cardiology, Faculty of Medicine &amp; Dentistry: Pediatrics Department, Stollery Children\u2019s Hospital, Edmonton, Canada (J.A.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5871-0265","authenticated-orcid":true,"given":"John R.","family":"Giudicessi","sequence":"additional","affiliation":[{"name":"Departments of Cardiovascular Medicine, Pediatric and Adolescent Medicine, and Molecular Pharmacology &amp; Experimental Therapeutics, Division of Heart Rhythm Services and Pediatric Cardiology, Windland Smith Rice Sudden Death Genomics Laboratory, Mayo Clinic, Rochester, MN (J.M.B., K.B.S., J.R.G., M.J.A.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5276-1475","authenticated-orcid":true,"given":"Sally-Ann B.","family":"Clur","sequence":"additional","affiliation":[{"name":"Member of the European Reference Network for rare, low prevalence and complex diseases of the heart: ERN GUARD-Heart (ERN GUARDHEART; I.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., V.B., A.L., C.v.d.W., A.A.M.W.)."},{"name":"Department of Pediatric Cardiology, Emma Children\u2019s Hospital, Amsterdam UMC, University of Amsterdam, The Netherlands (P.J.P., S.-A.B.C., N.A.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nico A.","family":"Blom","sequence":"additional","affiliation":[{"name":"Member of the European Reference Network for rare, low prevalence and complex diseases of the heart: ERN GUARD-Heart (ERN GUARDHEART; I.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., V.B., A.L., C.v.d.W., A.A.M.W.)."},{"name":"Department of Pediatric Cardiology, Emma Children\u2019s Hospital, Amsterdam UMC, University of Amsterdam, The Netherlands (P.J.P., S.-A.B.C., N.A.B.)."},{"name":"Department of Pediatric Cardiology, Willem-Alexander Children\u2019s Hospital, Leiden University Medical Centre, The Netherlands (N.A.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9828-4459","authenticated-orcid":true,"given":"Michael","family":"Tanck","sequence":"additional","affiliation":[{"name":"Amsterdam 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.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8123-4842","authenticated-orcid":true,"given":"Fabrice","family":"Extramiana","sequence":"additional","affiliation":[{"name":"Member of the European Reference Network for rare, low prevalence and complex diseases of the heart: ERN GUARD-Heart (ERN GUARDHEART; I.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., V.B., A.L., C.v.d.W., A.A.M.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6125-0789","authenticated-orcid":true,"given":"Koichi","family":"Kato","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Shiga University of Medical Science, Otsu, Japan (S.O., K.K., M.H.), National Cerebral and Cardiovascular Centre, Suita, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4106-5946","authenticated-orcid":true,"given":"Julien","family":"Barc","sequence":"additional","affiliation":[{"name":"Member of the European Reference Network for rare, low prevalence and complex diseases of the heart: ERN GUARD-Heart (ERN GUARDHEART; I.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., V.B., A.L., C.v.d.W., A.A.M.W.)."},{"name":"Universit\u00e9 de Nantes, CNRS, INSERM, l\u2019institut du thorax, Nantes, France (J.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Borggrefe","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Nantes, CNRS, INSERM, l\u2019institut du thorax, Nantes, France (J.B.)."},{"name":"Department of Medicine, University Medical Center Mannheim, Germany (M.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8731-2853","authenticated-orcid":true,"given":"Elijah R.","family":"Behr","sequence":"additional","affiliation":[{"name":"German Center for Cardiovascular Research (DZHK), Partner Site Heidelberg\/Mannheim (M.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgia","family":"Sarquella-Brugada","sequence":"additional","affiliation":[{"name":"Member of the European Reference Network for rare, low prevalence and complex diseases of the heart: ERN GUARD-Heart (ERN GUARDHEART; I.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., V.B., A.L., C.v.d.W., A.A.M.W.)."},{"name":"Pediatric Arrhythmias, Inherited Cardiac Diseases and Sudden Death Unit, Hospital Sant Joan de D\u00e9u, Spain; Medical Science Department, School of Medicine, Universitat de Girona, Spain (G.S.-B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3895-9316","authenticated-orcid":true,"given":"Jacob","family":"Tfelt-Hansen","sequence":"additional","affiliation":[{"name":"Member of the European Reference Network for rare, low prevalence and complex diseases of the heart: ERN GUARD-Heart (ERN GUARDHEART; I.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., V.B., A.L., C.v.d.W., A.A.M.W.)."},{"name":"Department of Cardiology, Rigshospitalet, Copenhagen, Denmark (J.T.-H.)."},{"name":"Department of Forensic Medicine, Faculty of Medical Sciences, University of Copenhagen, Denmark (J.T.-H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3608-4210","authenticated-orcid":true,"given":"Esther","family":"Zorio","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Hospital Universitario y Polit\u00e9cnico La Fe, Valencia, Spain (E.Z.)."},{"name":"Center for Biomedical Network Research on Cardiovascular Diseases (CIBERCV), Madrid, Spain (E.Z.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heikki","family":"Swan","sequence":"additional","affiliation":[{"name":"Heart and Lung Centre, Helsinki University Hospital and Helsinki University, Finland (H.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janneke A.E.","family":"Kammeraad","sequence":"additional","affiliation":[{"name":"Department of Pediatric Cardiology, Erasmus MC - Sophia, Rotterdam, The Netherlands (J.A.E.K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7982-1586","authenticated-orcid":true,"given":"Andrew D.","family":"Krahn","sequence":"additional","affiliation":[{"name":"Center for Cardiovascular Innovation, Division of Cardiology (T.M.R., A.D.K.), University of British Columbia, Vancouver, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2826-8562","authenticated-orcid":true,"given":"Andrew","family":"Davis","sequence":"additional","affiliation":[{"name":"The Royal Children\u2019s Hospital, Melbourne, Australia (A.D.)."},{"name":"Murdoch Children\u2019s Research Institute and Department of Paediatrics, Melbourne University, Australia (A.D.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8348-9320","authenticated-orcid":true,"given":"Frederic","family":"Sacher","sequence":"additional","affiliation":[{"name":"LIRYC Institute, Bordeaux University Hospital, Bordeaux University, France (F.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0367-1048","authenticated-orcid":true,"given":"Peter J.","family":"Schwartz","sequence":"additional","affiliation":[{"name":"Member of the European Reference Network for rare, low prevalence and complex diseases of the heart: ERN GUARD-Heart (ERN GUARDHEART; I.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., V.B., A.L., C.v.d.W., A.A.M.W.)."},{"name":"Istituto Auxologico Italiano, IRCCS, Center for Cardiac Arrhythmias of Genetic Origin, Milan, Italy (P.J.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0268-6723","authenticated-orcid":true,"given":"Jason D.","family":"Roberts","sequence":"additional","affiliation":[{"name":"Section of Cardiac Electrophysiology, Division of Cardiology, Department of Medicine, Western University, London, Ontario, Canada (J.D.R.)."},{"name":"Population Health Research Institute, Hamilton Health Sciences, and McMaster University, Hamilton, Ontario, Canada (J.D.R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3653-0412","authenticated-orcid":true,"given":"Jonathan R.","family":"Skinner","sequence":"additional","affiliation":[{"name":"Cardiac Inherited Disease Group New Zealand, Green Lane Paediatric and Congenital Cardiac Services, Starship Children\u2019s Hospital, Auckland, New Zealand (J.R.S.)."},{"name":"Department of Paediatrics Child and Youth Health, The University of Auckland, New Zealand (J.R.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1493-2998","authenticated-orcid":true,"given":"Maarten P.","family":"van den Berg","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University of Groningen, University Medical Centre Groningen, The Netherlands (M.P.v.d.B)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1529-9872","authenticated-orcid":true,"given":"Prince J.","family":"Kannankeril","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Monroe Carell Jr Children\u2019s Hospital at Vanderbilt, Vanderbilt University Medical Centre, Nashville, TN (P.J.K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1888-373X","authenticated-orcid":true,"given":"Fabrizio","family":"Drago","sequence":"additional","affiliation":[{"name":"Member of the European Reference Network for rare, low prevalence and complex diseases of the heart: ERN GUARD-Heart (ERN GUARDHEART; 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