Catecholaminergic polymorphic ventricular tachycardia mediated by ryanodine receptor 2: a validated risk stratification
Background and Aims Patients with catecholaminergic polymorphic ventricular tachycardia (CPVT) are at risk for potentially life-threatening arrhythmic events (AEs) even while treated with beta-blockers. The aim was to develop a model for individualized prediction of AEs in patients with RYR2-mediate...
| Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | article |
| Status: | Published version |
| Publication Date: | 2025 |
| Country: | España |
| Institution: | Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO) |
| Repository: | r-FISABIO. Repositorio Institucional de Producción Científica |
| OAI Identifier: | oai:fisabio.fundanetsuite.com:p20302 |
| Online Access: | https://fisabio.portalinvestigacion.com/publicaciones/20302 |
| Access Level: | Open access |
| Keyword: | Catecholaminergic polymorphic ventricular tachycardia beta-Blockers Risk stratification Sudden cardiac death Ventricular arrhythmias |
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Catecholaminergic polymorphic ventricular tachycardia mediated by ryanodine receptor 2: a validated risk stratificationLieve, KVvan der Werf, CKallas, DDenjoy, IBos, JMAiba, TBehr, ERvan den Berg, MPBergeman, ATBlom, NABorggrefe, MBrugada, RMora, LMCChorin, ECrotti, LDavis, ADrago, FDusi, VExtramiana, FFranciosi, SGiudicessi, JRLlopis, FAGHaugaa, KHvan den Heuvel, FHorie, MIngles, JKammeraad, JKannankeril, PJKhan, HRKrahn, ADMacIntyre, CMaltret, AMarjamaa, AOhno, SPeltenburg, PJPerez, GJProbst, VRoberts, JDRobyns, TRootwelt-Norberg, CNoguer, FRIRoston, TMRydberg, ASacher, FSarquella-Brugada, GSchwartz, PJSemsarian, CShimizu, WStarling, LSumitomo, NSkinner, JRTavacova, TTfelt-Hansen, JTill, JAYap, SCWada, YWangüemert, FZorio, EAckerman, MJLeenhardt, ASanatani, STanck, MWWilde, AACatecholaminergic polymorphic ventricular tachycardiabeta-BlockersRisk stratificationSudden cardiac deathVentricular arrhythmiasBackground and Aims Patients with catecholaminergic polymorphic ventricular tachycardia (CPVT) are at risk for potentially life-threatening arrhythmic events (AEs) even while treated with beta-blockers. The aim was to develop a model for individualized prediction of AEs in patients with RYR2-mediated CPVT on beta-blocker monotherapy.Methods The derivation and independent validation cohorts included 743 and 129 patients, respectively. AEs were defined as arrhythmic syncope, appropriate implantable cardioverter-defibrillator 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.Results A total of 102 (13.7%) patients in the derivation cohort and 24 (18.6%) patients in the validation cohort experienced >= 1 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 beta-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) 0.62-0.72] and 0.59 (95% CI 0.48-0.71), respectively. For nf/fAEs, ventricular arrhythmia severity before beta-blocker initiation was a fourth independent predictor, and C-indices of the models in the derivation and validation cohorts were 0.74 (95% CI 0.68-0.80) and 0.60 (95% CI 0.47-0.72), respectively. In the derivation cohort, calibration slopes were 1.00 (95% CI 0.59-1.41) for AE and 1.00 (95% CI 0.69-1.32) for nf/fAE.Conclusions These externally validated risk prediction models using clinical parameters accurately distinguished CPVT patients on beta-blocker monotherapy at low and high risk for future AEs while treated with beta-blockers. These models provide guidance for implementation of clinical management therapies to prevent AEs in patients with CPVT.OXFORD UNIV PRESS2025info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://fisabio.portalinvestigacion.com/publicaciones/20302EUROPEAN HEART JOURNALISSN: 0195668XISSNe: 15229645reponame:r-FISABIO. Repositorio Institucional de Producción Científicainstname:Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO)Inglésinfo:eu-repo/semantics/openAccessoai:fisabio.fundanetsuite.com:p203022026-06-11T12:45:17Z |
| dc.title.none.fl_str_mv |
Catecholaminergic polymorphic ventricular tachycardia mediated by ryanodine receptor 2: a validated risk stratification |
| title |
Catecholaminergic polymorphic ventricular tachycardia mediated by ryanodine receptor 2: a validated risk stratification |
| spellingShingle |
Catecholaminergic polymorphic ventricular tachycardia mediated by ryanodine receptor 2: a validated risk stratification Lieve, KV Catecholaminergic polymorphic ventricular tachycardia beta-Blockers Risk stratification Sudden cardiac death Ventricular arrhythmias |
| title_short |
Catecholaminergic polymorphic ventricular tachycardia mediated by ryanodine receptor 2: a validated risk stratification |
| title_full |
Catecholaminergic polymorphic ventricular tachycardia mediated by ryanodine receptor 2: a validated risk stratification |
| title_fullStr |
Catecholaminergic polymorphic ventricular tachycardia mediated by ryanodine receptor 2: a validated risk stratification |
| title_full_unstemmed |
Catecholaminergic polymorphic ventricular tachycardia mediated by ryanodine receptor 2: a validated risk stratification |
| title_sort |
Catecholaminergic polymorphic ventricular tachycardia mediated by ryanodine receptor 2: a validated risk stratification |
| dc.creator.none.fl_str_mv |
Lieve, KV van der Werf, C Kallas, D Denjoy, I Bos, JM Aiba, T Behr, ER van den Berg, MP Bergeman, AT Blom, NA Borggrefe, M Brugada, R Mora, LMC Chorin, E Crotti, L Davis, A Drago, F Dusi, V Extramiana, F Franciosi, S Giudicessi, JR Llopis, FAG Haugaa, KH van den Heuvel, F Horie, M Ingles, J Kammeraad, J Kannankeril, PJ Khan, HR Krahn, AD MacIntyre, C Maltret, A Marjamaa, A Ohno, S Peltenburg, PJ Perez, GJ Probst, V Roberts, JD Robyns, T Rootwelt-Norberg, C Noguer, FRI Roston, TM Rydberg, A Sacher, F Sarquella-Brugada, G Schwartz, PJ Semsarian, C Shimizu, W Starling, L Sumitomo, N Skinner, JR Tavacova, T Tfelt-Hansen, J Till, JA Yap, SC Wada, Y Wangüemert, F Zorio, E Ackerman, MJ Leenhardt, A Sanatani, S Tanck, MW Wilde, AA |
| author |
Lieve, KV |
| author_facet |
Lieve, KV van der Werf, C Kallas, D Denjoy, I Bos, JM Aiba, T Behr, ER van den Berg, MP Bergeman, AT Blom, NA Borggrefe, M Brugada, R Mora, LMC Chorin, E Crotti, L Davis, A Drago, F Dusi, V Extramiana, F Franciosi, S Giudicessi, JR Llopis, FAG Haugaa, KH van den Heuvel, F Horie, M Ingles, J Kammeraad, J Kannankeril, PJ Khan, HR Krahn, AD MacIntyre, C Maltret, A Marjamaa, A Ohno, S Peltenburg, PJ Perez, GJ Probst, V Roberts, JD Robyns, T Rootwelt-Norberg, C Noguer, FRI Roston, TM Rydberg, A Sacher, F Sarquella-Brugada, G Schwartz, PJ Semsarian, C Shimizu, W Starling, L Sumitomo, N Skinner, JR Tavacova, T Tfelt-Hansen, J Till, JA Yap, SC Wada, Y Wangüemert, F Zorio, E Ackerman, MJ Leenhardt, A Sanatani, S Tanck, MW Wilde, AA |
| author_role |
author |
| author2 |
van der Werf, C Kallas, D Denjoy, I Bos, JM Aiba, T Behr, ER van den Berg, MP Bergeman, AT Blom, NA Borggrefe, M Brugada, R Mora, LMC Chorin, E Crotti, L Davis, A Drago, F Dusi, V Extramiana, F Franciosi, S Giudicessi, JR Llopis, FAG Haugaa, KH van den Heuvel, F Horie, M Ingles, J Kammeraad, J Kannankeril, PJ Khan, HR Krahn, AD MacIntyre, C Maltret, A Marjamaa, A Ohno, S Peltenburg, PJ Perez, GJ Probst, V Roberts, JD Robyns, T Rootwelt-Norberg, C Noguer, FRI Roston, TM Rydberg, A Sacher, F Sarquella-Brugada, G Schwartz, PJ Semsarian, C Shimizu, W Starling, L Sumitomo, N Skinner, JR Tavacova, T Tfelt-Hansen, J Till, JA Yap, SC Wada, Y Wangüemert, F Zorio, E Ackerman, MJ Leenhardt, A Sanatani, S Tanck, MW Wilde, AA |
| author2_role |
author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author |
| dc.subject.none.fl_str_mv |
Catecholaminergic polymorphic ventricular tachycardia beta-Blockers Risk stratification Sudden cardiac death Ventricular arrhythmias |
| topic |
Catecholaminergic polymorphic ventricular tachycardia beta-Blockers Risk stratification Sudden cardiac death Ventricular arrhythmias |
| description |
Background and Aims Patients with catecholaminergic polymorphic ventricular tachycardia (CPVT) are at risk for potentially life-threatening arrhythmic events (AEs) even while treated with beta-blockers. The aim was to develop a model for individualized prediction of AEs in patients with RYR2-mediated CPVT on beta-blocker monotherapy.Methods The derivation and independent validation cohorts included 743 and 129 patients, respectively. AEs were defined as arrhythmic syncope, appropriate implantable cardioverter-defibrillator 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.Results A total of 102 (13.7%) patients in the derivation cohort and 24 (18.6%) patients in the validation cohort experienced >= 1 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 beta-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) 0.62-0.72] and 0.59 (95% CI 0.48-0.71), respectively. For nf/fAEs, ventricular arrhythmia severity before beta-blocker initiation was a fourth independent predictor, and C-indices of the models in the derivation and validation cohorts were 0.74 (95% CI 0.68-0.80) and 0.60 (95% CI 0.47-0.72), respectively. In the derivation cohort, calibration slopes were 1.00 (95% CI 0.59-1.41) for AE and 1.00 (95% CI 0.69-1.32) for nf/fAE.Conclusions These externally validated risk prediction models using clinical parameters accurately distinguished CPVT patients on beta-blocker monotherapy at low and high risk for future AEs while treated with beta-blockers. These models provide guidance for implementation of clinical management therapies to prevent AEs in patients with CPVT. |
| publishDate |
2025 |
| dc.date.none.fl_str_mv |
2025 |
| dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion |
| format |
article |
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publishedVersion |
| dc.identifier.none.fl_str_mv |
https://fisabio.portalinvestigacion.com/publicaciones/20302 |
| url |
https://fisabio.portalinvestigacion.com/publicaciones/20302 |
| dc.language.none.fl_str_mv |
Inglés |
| language_invalid_str_mv |
Inglés |
| dc.rights.none.fl_str_mv |
info:eu-repo/semantics/openAccess |
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openAccess |
| dc.publisher.none.fl_str_mv |
OXFORD UNIV PRESS |
| publisher.none.fl_str_mv |
OXFORD UNIV PRESS |
| dc.source.none.fl_str_mv |
EUROPEAN HEART JOURNAL ISSN: 0195668X ISSNe: 15229645 reponame:r-FISABIO. Repositorio Institucional de Producción Científica instname:Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO) |
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Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO) |
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r-FISABIO. Repositorio Institucional de Producción Científica |
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r-FISABIO. Repositorio Institucional de Producción Científica |
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1869403123896811520 |
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15.811543 |