Why the study?
Patients with catecholaminergic polymorphic ventricular tachycardia remain at risk for life-threatening arrhythmic events despite β-blocker therapy, prompting development of an individualized risk prediction model.
Can clinical parameters accurately predict the risk of future arrhythmic events in patients with RYR2-mediated CPVT treated with β-blocker monotherapy?
Cohort (n=872)
Yes
Can clinical parameters accurately predict the risk of future arrhythmic events in patients with RYR2-mediated CPVT treated with β-blocker monotherapy?
Effect estimate: optimism-corrected C-index 0.67 (95% CI 0.62-0.72)
A validated clinical prediction model efficiently stratifies CPVT patients on β-blockers into low, intermediate, or high risk for subsequent arrhythmic events, helping guide the targeted deployment of adjunctive therapies like flecainide or sympathetic denervation.
May inform risk stratification in RYR2-mediated CPVT on β-blockers; leaves open prospective validation before clinical use.
Background and Aims Patients with catecholaminergic polymorphic ventricular tachycardia (CPVT) are at risk for potentially life-threatening arrhythmic events (AEs) even while treated with β-blockers. The aim was to develop a model for individualized prediction of AEs in patients with RYR2-mediated CPVT on β-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 β-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 β-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 β-blocker monotherapy at low and high risk for future AEs while treated with β-blockers. These models provide guidance for implementation of clinical management therapies to prevent AEs in patients with CPVT.
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A 2025 study conducted a cohort in Catecholaminergic polymorphic ventricular tachycardia (CPVT) (n=872). Clinical risk prediction model (age at β-blocker initiation, prior sudden cardiac arrest, prior arrhythmic syncope) was evaluated on Arrhythmic events (arrhythmic syncope, appropriate implantable cardioverter–defibrillator shock, sudden cardiac arrest, and sudden cardiac death) (optimism-corrected C-index 0.67, 95% CI 0.62-0.72).
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