Catecholaminergic polymorphic ventricular tachycardia mediated by ryanodine receptor 2: a validated risk stratification

Author(s):
Lieve, K.V.; Werf, C. van der; Kallas, D.; Denjoy, I.; Bos, J.M.; Aiba, T.; Behr, E.R.; Berg, M.P. van den; Bergeman, A.T.; Blom, N.A. (0000-0002-4823-6974); Borggrefe, M.; Brugada, R.; Mora, L.M.C.; Chorin, E.; Crotti, L.; Davis, A.; Drago, F.; Dusi, V.; Extramiana, F.; Franciosi, S.; Giudicessi, J.R.; Llopis, F.A.G.; Haugaa, K.H.; Heuvel, F. van den; Horie, M.; Ingles, J.; Kammeraad, J.; Kannankeril, P.J.; Khan, H.R.; Krahn, A.D.; MacIntyre, C.; Maltret, A.; Marjamaa, A.; Ohno, S.; Peltenburg, P.J.; Perez, G.J.; Probst, V.; Roberts, J.D.; Robyns, T.; Rootwelt-Norberg, C.; Noguer, F.R.I.; Roston, T.M.; Rydberg, A.; Sacher, F.; Sarquella-Brugada, G.; Schwartz, P.J.; Semsarian, C.; Shimizu, W.; Starling, L.; Sumitomo, N.; Skinner, J.R.; Tavacova, T.; Tfelt-Hansen, J.; Till, J.A.; Yap, S.C.; Wada, Y.; Wangüemert, F.; Zorio, E.; Ackerman, M.J.; Leenhardt, A.; Sanatani, S.; Tanck, M.W.; Wilde, A.A.
Published
2025
Publication type
Article / Letter to editor

Abstract

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.

Catecholaminergic polymorphic ventricular tachycardiabeta-BlockersRisk stratificationSudden cardiac deathVentricular arrhythmias
Date issued
2025-12-19
Language
English
Publisher
OXFORD UNIV PRESS
Is part of
European Heart Journal
hdl
1887/4300121
doi
10.1093/eurheartj/ehaf965