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The aim was to develop a model for individualized prediction of AEs in patients with RYR2-mediated CPVT on \u03b2-blocker monotherapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The derivation and independent validation cohorts included 743 and 129 patients, respectively. AEs were defined as arrhythmic syncope, appropriate implantable cardioverter\u2013defibrillator shock, sudden cardiac arrest (SCA), and sudden cardiac death. Near-fatal or fatal AEs (nf\/fAEs) included all AEs except for arrhythmic syncope. Prediction models using Cox regression were developed and internally and externally validated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 102 (13.7%) patients in the derivation cohort and 24 (18.6%) patients in the validation cohort experienced \u22651 AE over a median follow-up of 5.1 [interquartile range (IQR), 7.7] and 2.4 (IQR, 4.4) years, respectively. Predictors of AE were arrhythmic syncope or SCA prior to diagnosis and age at \u03b2-blocker initiation. In the derivation and validation cohorts, the optimism-corrected C-indices of the models for AE were 0.67 [95% confidence interval (CI) 0.62\u20130.72] and 0.59 (95% CI 0.48\u20130.71), respectively. For nf\/fAEs, ventricular arrhythmia severity before \u03b2-blocker initiation was a fourth independent predictor, and C-indices of the models in the derivation and validation cohorts were 0.74 (95% CI 0.68\u20130.80) and 0.60 (95% CI 0.47\u20130.72), respectively. In the derivation cohort, calibration slopes were 1.00 (95% CI 0.59\u20131.41) for AE and 1.00 (95% CI 0.69\u20131.32) for nf\/fAE.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These externally validated risk prediction models using clinical parameters accurately distinguished CPVT patients on \u03b2-blocker monotherapy at low and high risk for future AEs while treated with \u03b2-blockers. These models provide guidance for implementation of clinical management therapies to prevent AEs in patients with CPVT.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/eurheartj\/ehaf965","type":"journal-article","created":{"date-parts":[[2025,11,9]],"date-time":"2025-11-09T12:47:47Z","timestamp":1762692467000},"page":"4606-4617","source":"Crossref","is-referenced-by-count":5,"title":["Catecholaminergic polymorphic ventricular tachycardia mediated by ryanodine receptor 2: a validated risk stratification"],"prefix":"10.1093","volume":"47","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3960-5552","authenticated-orcid":false,"given":"Krystien V","family":"Lieve","sequence":"first","affiliation":[{"name":"Heart Center, Department of Clinical and Experimental Cardiology, Amsterdam UMC location University of Amsterdam , Meibergdreef 9, 1105 AZ, Amsterdam ,","place":["The Netherlands"]},{"name":"Heart Failure and Arrhythmias, Amsterdam Cardiovascular Sciences , Meibergdreef 9, Amsterdam 1105 AZ ,","place":["The Netherlands"]},{"name":"Member of the European Reference Network for Rare, Low Prevalence and Complex Diseases of the Heart: ERN GUARD-Heart (ERN GUARD-Heart ; http:\/\/guardheart.ern-net.eu )"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8703-8527","authenticated-orcid":false,"given":"Christian","family":"van der Werf","sequence":"additional","affiliation":[{"name":"Heart Center, Department of Clinical and Experimental Cardiology, Amsterdam UMC location University of Amsterdam , Meibergdreef 9, 1105 AZ, Amsterdam ,","place":["The Netherlands"]},{"name":"Heart Failure and Arrhythmias, Amsterdam Cardiovascular Sciences , Meibergdreef 9, Amsterdam 1105 AZ ,","place":["The Netherlands"]},{"name":"Member of the European Reference Network for Rare, Low Prevalence and Complex Diseases of the Heart: ERN GUARD-Heart (ERN GUARD-Heart ; http:\/\/guardheart.ern-net.eu )"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7438-0873","authenticated-orcid":false,"given":"Dania","family":"Kallas","sequence":"additional","affiliation":[{"name":"BC Children's Hospital , Division of Cardiology, Vancouver, British Columbia ,","place":["Canada"]},{"name":"Department of Pediatrics, University of British Columbia , Vancouver, British Columbia ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1786-9461","authenticated-orcid":false,"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 GUARD-Heart ; 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Medizinische Klinik, University Medical Center Mannheim, University of Heidelberg , Mannheim ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6607-3032","authenticated-orcid":false,"given":"Ramon","family":"Brugada","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Cardiovasculares (CIBERCV) , Madrid ,","place":["Spain"]},{"name":"Cardiovascular Genetics Center, Institut D\u2019Investigaci\u00f3 Biom\u00e8dica Girona (IDIBGI), University of Girona , Salt ,","place":["Spain"]},{"name":"Medical Science Department, School of Medicine, University of Girona , Girona ,","place":["Spain"]},{"name":"Cardiology Service, Hospital Josep Trueta , Girona ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7314-9779","authenticated-orcid":false,"given":"Lidia Mar\u00eda","family":"Carrillo Mora","sequence":"additional","affiliation":[{"name":"Member of the European Reference Network for Rare, Low Prevalence and Complex Diseases of the Heart: ERN GUARD-Heart (ERN GUARD-Heart ; http:\/\/guardheart.ern-net.eu )"},{"name":"Departamento de Medicina Interna, Universidad de Murcia , Ctra. 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,","place":["USA"]},{"name":"Department of Molecular Pharmacology & Experimental Therapeutics, Mayo Clinic , Rochester, MN ,","place":["USA"]},{"name":"Division of Heart Rhythm Services, Mayo Clinic , Rochester, MN ,","place":["USA"]},{"name":"Division of Pediatric Cardiology, Mayo Clinic , Rochester, MN ,","place":["USA"]},{"name":"Windland Smith Rice Genetic Heart Rhythm Clinic and Windland Smith Rice Sudden Death Genomics Laboratory, Mayo Clinic , Rochester, MN ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0064-4426","authenticated-orcid":false,"given":"Francisco \u00c1ngel","family":"Gonz\u00e1lez Llopis","sequence":"additional","affiliation":[{"name":"Cardiology Department, General University Hospital of Elda , Alicante ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4900-0453","authenticated-orcid":false,"given":"Kristina 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